STZ诱导的1型糖尿病大鼠急性心肌梗死后心脏结构和功能以及基因表达谱和细胞凋亡的时间依赖性变化
|
摘要
目的:研究链脲佐菌素(streptozotocin,STZ)诱导的1型糖尿病(diabetes mellitus,DM)大鼠急性心肌梗死(acute myocardial infarction,AMI)后的存活率、心脏结构和功能以及心肌纤维化时间依赖性变化。
方法:Sprague-Dawley(SD)大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗,在诱导前以及诱导后3天、7天、30天和70天记录体重、检测血糖并应用心肌透射电镜扫描观察糖尿病大鼠心肌超微结构的变化;结扎冠状动脉前降支,不进行再灌注治疗,计算大鼠在结扎后1天、7天、14天、28天和56天的存活率;应用超声心动图和血流动力学监测糖尿病大鼠在AMI后上述5个时间点的心脏功能;应用Masson's染色来定量评价其非梗死区心肌纤维化的程度。
结果:诱导糖尿病10周后,糖尿病大鼠的血糖显著高于非糖尿病组大鼠(489±28vs.112±13mg/dl,P＜0.001);同时其体重从第3日起与非糖尿病大鼠有显著差别,并且差异进行性加大,至10周时其体重显著低于非糖尿病大鼠(244.8±23.6 vs.516.3±48.6克,P＜0.001)。心肌电镜扫描观察到糖尿病组大鼠心肌细胞的各带结构不清,走行紊乱,核周围线粒体增多,线粒体周围糖原和脂滴聚集,线粒体肿胀。部分心肌纤维出现纤维溶解坏死,同时伴凝固性坏死。AMI后糖尿病大鼠存活率明显低于非糖尿病大鼠,非糖尿病组在对应时间点的存活率为82.9%(58/70)、80.0%(48/60)、80.0%(40/50)、77.5%(31/40)和76.7%(23/30),而糖尿病组在1天、7天、14天、28天和56天的存活率分别为67.2%(44/64,P＜0.05)、64.8%(35/54,P=NS)、61.4%(27/44,P＜0.05)、52.9%(18/34,P＜0.05)和41.7%(10/24,P＜0.05)。超声心动图和血流动力学监测显示,糖尿病大鼠AMI前存在舒张功能不全;AMI后两组大鼠心功能均明显下降,糖尿病大鼠心功能恶化更加显著(EF 37.3±5.4%vs.48.8±4.1%,P＜0.01 and FS 17.0±1.4%vs.23.7±2.5%,P＜0.05);左心室扩张更加明显(增加的LVEDD 47.5±5.2%vs.26.8±4.9%,P＜0.001);心肌纤维化染色发现糖尿病大鼠AMI28天和56天时非梗死区纤维化相对于非糖尿病大鼠更加明显(10.3%±1.5%vs.3.8%±0.9%,P＜0.001 and 17.5%±2.1%vs.9.8%±1.2%,P＜0.001)。
结论:一系列病理生理学改变显示,糖尿病大鼠AMI后易发心力衰竭的原因早期是由于严重的心脏舒张功能不全,晚期则是由于其心功能不全和心肌重塑加速所致。
目的:研究糖尿病与非糖尿病大鼠急性心肌梗死后基因表达的差异。
方法:SD大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗;结扎冠状动脉前降支,应用大鼠全基因序列的基因芯片、Real time-PCR来检测AMI后1天、7天、14天、28天和56天糖尿病大鼠左心室非梗死区基因表达的变化。
结果:AMI后,糖尿病大鼠与非糖尿病大鼠相比生存率明显降低,如前所述,病理生理学变化表明DM能够加速AMI后心肌重塑的进展。基因芯片分析显示随着时间的变化,两组大鼠基因表达显著不同,糖尿病大鼠AMI后左心室非梗死区心肌组织有1221个基因表达与非糖尿病大鼠显著不同,其中770个表达上调,451个表达下调;对差异基因进行功能分析发现其涵盖糖代谢、脂肪酸代谢、细胞外基质、凋亡、氧化还原和磷酸酶活性等诸多方面。无监督聚类分析发现糖尿病大鼠AMI后左心室非梗死区1-7天的基因表达变化和非糖尿病大鼠相似,14天时的基因表达变化与非糖尿病大鼠14和28天相似,而其28和56天的基因变化和非糖尿病大鼠56天相似,显示糖尿病大鼠AMI后重塑相关基因的表达谱提前1-2周。根据筛选条件,应用到无监督聚类分析的基因为164个,其中118个已经被命名,大部分被证实与心脏重构密切相关,例如富含亮氨酸的PPR模体(白介素-6信号通路)、原骨胶原Ⅰ型和Ⅲ型、纤维连接蛋白1、RT1,and TIMP-1等等。
结论:STZ诱导的1型糖尿病大鼠急性心肌梗死后心功能的恶化可能与相关基因表达谱的前移和过量表达有关。
目的:观察糖尿病大鼠AMI后梗死周边区的心肌细胞凋亡的时间依赖性变化。
方法:SD大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗;结扎冠状动脉前降支,取材,应用免疫细胞化学Tunel法检测细胞凋亡。取材左心室梗死周边区组织(距离心肌梗死边缘2.5mm范围),应用免疫印迹(Western blot)法半定量分析凋亡相关蛋白Bax和Bcl-2蛋白水平的含量;应用实时定量PCR(real time-PCR)法定量分析结缔组织生长因子(CTGF)和caspase-3mRNA水平的表达。
结果:研究显示STZ诱导10周后,糖尿病大鼠心肌组织凋亡指数显著高于非糖尿病大鼠(3.2±0.5 vs.1.4±0.3,P＜0.01);在急性心肌梗死后的1天(20.1±1.8 vs.16.9±1.5,P＜0.05)、7天(16.1±1.7 vs.12.9±1.3,P＜0.01)、14天(16.1±1.7 vs.13.1±1.4,P＜0.05)、28天(15.2±1.8 vs.11.9±1.5,P＜0.01]和56天(16.3±1.6 vs.9.6±1.2,P＜0.001)时其左心室梗死周边区心肌细胞进行性凋亡,凋亡指数(括号中数值)显著高于非糖尿病大鼠。和非糖尿病组大鼠相比,Western blot法半定量分析显示糖尿病大鼠急性心肌梗死后1天、7天、28天和56天促凋亡蛋白Bax水平显著增加(P＜0.001);而抑凋亡蛋白Bcl-2水平在AMI后1天、14天、28天和56天显著降低(P＜0.001)。实时定量PCR结果显示CTGF和caspase-3mRNA的水平较非糖尿病大鼠显著增加。
结论:与非糖尿病大鼠相比,糖尿病大鼠急性心肌梗死后左心室梗死周边区的细胞进行性凋亡可能会导致其左心室扩大和心肌纤维化的程度显著较高,从而更加容易发生心力衰竭;其Bax和Bcl-2的蛋白水平提示其细胞凋亡通路可能包含线粒体凋亡通路。
Objective:In spite of numerous studies in diabetic animal models,to our knowledge,myocardial performance,especially time course study was never performed in untreated diabetic myocardial infarction(MI) rat model without reperfusion.
Methods:In the present study,myocardial function and structure changes of myocardium were examined in untreated streptozotocin(STZ)-induced diabetic MI rat model without perfusion. DM was induced with a single intraperitoneal injection of STZ(65 mg/kg),and body weight was recorded and serum glucose levels were determined at baseline,day 3,day 7,day 30 and day 70 after STZ injection by using One Touch Sure Step test strips and meter(Life Scan,Johnson & Johnson,Warren NJ,USA).Ten weeks after DM induction without any therapy,the left anterior descending coronary artery of diabetic Sprague-Dawley rats was ligated to induce no-reperfusion MI model Tissue structure of myocardium,two-dimensional echocardiography,and hemodynamic studies were utilized to monitor the time course changes of above relating parameters up to 56 days.
Results:Ten weeks after DM established,serum glucose levels were significantly higher in the diabetic rats(489±28mg/dl) than in the non-diabetic animals(112±13mg/dl,P＜0.001).Body weights were significantly lower in the diabetic rats(244.8±23.6g) than that of non-diabetic ones (516.3±48.6g,P＜0.001).TEM examination showed that the heart of diabetic rats contained increased lipid droplets and glycogen particles around mitochondria and scattered mitochondrial damage(swelling and disrupted cristae);in addition,cardiac muscle fibers were identified to be crumbly in the majority of the diabetic rats,and the basal lamina of regional small vessels was thicker in some regions.After AMI,Diabetic rats experienced lower survival rate in both acute phase(1,7 and 14 days) and chronic phase(28 and 56 days) compared with non-diabetic rats at corresponding time points.During 56 days after myocardial infarction,worse left ventricular function(EF 37.3±5.4 vs.48.8±4.1,P＜0.01 and FS 17.0±1.4 vs.23.7±2.5,P＜0.05) and larger the left ventricular diameter(increased LVEDD 47.5±5.2%vs.26.8±4.9%,P＜0.001) were identified in diabetic rats than in non-diabetics.Furthermore,diabetic rats showed more serious myocardial fibrosis by quantification of fibrosis area in the remote zone of left ventricular free wall compared with non-diabetic ones at 28 and 56 days after MI(Masson's quantitation 10.3%±1.5%vs.3.8%±0.9%,P＜0.001 and 17.5%±2.1%vs.9.8%±1.2%,P＜0.001).
Conclusion:The different patterns of the pathophysiologic changes in the untreated STZ-induced diabetic MI rat model without reperfusion might suggest that in the early phase after AMI,LV diastolic dysfunction may account for the higher incidence of HF and death,while in the prolonged phase,both LV dysfunction and accelerated cardiac remodeling can be the motivation.
Objective:To study the time-dependent effects of genetic changes in untreated Streptozotocin (STZ)-induced diabetic rat with MI.
Methods:The left anterior descending coronary arteries were ligated 10 weeks after DM induction without any therapy and reperfusion.Microarray analysis and real time-PCR were utilized to monitor the time-dependent genetic changes in the remote zone of LV up to 56 days.
Results:The gene expression related to cardiac remodeling in the remote zone was quite different as time elapses between both groups.Total 1221 genes were found to be differentially expressed between diabetics and non-diabetics,770 unregulated and 451 downregulated, involving in glucose metabolism,fatty acid metabolism,extracellular matrix,apoptosis, oxido-reductase activity,phosphoprotein phosphatase activity,etc.The gene expression at 1 and 7 days post acute MI in diabetic and non-diabetic group was similar,while such changes at day 14 in diabetic rats were comparable to both 14 and 28 days in non-diabetic rats;moreover,the pattern of gene expression at day 28 and 56 in diabetic rats was similar to the ones at day 56 in non-diabetic rats,which may indicate that upregulation of the genes was found one-two weeks earlier in diabetic rats than in non-diabetic rats.In primary examination,164 genes(118 named) were found to be candidates for hierarchical analysis,such as leucine-rich PPR-motif containing (interleukin-6 signaling pathway),procollagen typeⅠandⅢ,fibronectin-1,RT1,and TIMP-1,etc.
Conclusion:The present data support that diabetes upregulates remodeling-related gene,which may be responsible for the worse outcomes in diabetes than in non-diabetes after myocardial infarction.
Objective:To examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.
Methods:Ten weeks after intravenous streptozotocin(diabetic groups) or citrate buffer(controls) injection,myocardial infarction was produced by ligation of left descending coronary artery.Level of cardiomyocyte apoptosis was quantified by TUNEL method;Bax and Bcl-2 proteins were determined by western blot method;CTGF and caspase-3 were quantitated by real time-PCR.
Results:The number of apoptotic cardiomyocytes was higher in diabetic than in non-diabetic rats after 10 weeks of DM induction(apototic index,3.2±0.5 vs.1.4±0.3,P<0.01).At 1d(20.1±1.8 vs.16.9±1.5,P<0.05),7d(16.1±1.7 vs.12.9±1.3,P<0.01),14d(16.1±1.7 vs.13.1±1.4,P<0.05), 28d(15.2±1.8 vs.11.9±1.5,P<0.01) and 56d(16.3±1.6 vs.9.6±1.2,P<0.001) after myocardial infarction,the apoptotic indices in the border zone of infarction area was higher in the diabetic as compared to non-diabetic rats.Correspondingly,Bax,connective tissue growth factor and caspase-3 expression were increased in diabetic compared with non-diabetic rats with myocardial infarction,whereas Bcl-2 expression was decreased.
Conclusion:Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.
方法:Sprague-Dawley(SD)大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗,在诱导前以及诱导后3天、7天、30天和70天记录体重、检测血糖并应用心肌透射电镜扫描观察糖尿病大鼠心肌超微结构的变化;结扎冠状动脉前降支,不进行再灌注治疗,计算大鼠在结扎后1天、7天、14天、28天和56天的存活率;应用超声心动图和血流动力学监测糖尿病大鼠在AMI后上述5个时间点的心脏功能;应用Masson's染色来定量评价其非梗死区心肌纤维化的程度。
结果:诱导糖尿病10周后,糖尿病大鼠的血糖显著高于非糖尿病组大鼠(489±28vs.112±13mg/dl,P＜0.001);同时其体重从第3日起与非糖尿病大鼠有显著差别,并且差异进行性加大,至10周时其体重显著低于非糖尿病大鼠(244.8±23.6 vs.516.3±48.6克,P＜0.001)。心肌电镜扫描观察到糖尿病组大鼠心肌细胞的各带结构不清,走行紊乱,核周围线粒体增多,线粒体周围糖原和脂滴聚集,线粒体肿胀。部分心肌纤维出现纤维溶解坏死,同时伴凝固性坏死。AMI后糖尿病大鼠存活率明显低于非糖尿病大鼠,非糖尿病组在对应时间点的存活率为82.9%(58/70)、80.0%(48/60)、80.0%(40/50)、77.5%(31/40)和76.7%(23/30),而糖尿病组在1天、7天、14天、28天和56天的存活率分别为67.2%(44/64,P＜0.05)、64.8%(35/54,P=NS)、61.4%(27/44,P＜0.05)、52.9%(18/34,P＜0.05)和41.7%(10/24,P＜0.05)。超声心动图和血流动力学监测显示,糖尿病大鼠AMI前存在舒张功能不全;AMI后两组大鼠心功能均明显下降,糖尿病大鼠心功能恶化更加显著(EF 37.3±5.4%vs.48.8±4.1%,P＜0.01 and FS 17.0±1.4%vs.23.7±2.5%,P＜0.05);左心室扩张更加明显(增加的LVEDD 47.5±5.2%vs.26.8±4.9%,P＜0.001);心肌纤维化染色发现糖尿病大鼠AMI28天和56天时非梗死区纤维化相对于非糖尿病大鼠更加明显(10.3%±1.5%vs.3.8%±0.9%,P＜0.001 and 17.5%±2.1%vs.9.8%±1.2%,P＜0.001)。
结论:一系列病理生理学改变显示,糖尿病大鼠AMI后易发心力衰竭的原因早期是由于严重的心脏舒张功能不全,晚期则是由于其心功能不全和心肌重塑加速所致。
目的:研究糖尿病与非糖尿病大鼠急性心肌梗死后基因表达的差异。
方法:SD大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗;结扎冠状动脉前降支,应用大鼠全基因序列的基因芯片、Real time-PCR来检测AMI后1天、7天、14天、28天和56天糖尿病大鼠左心室非梗死区基因表达的变化。
结果:AMI后,糖尿病大鼠与非糖尿病大鼠相比生存率明显降低,如前所述,病理生理学变化表明DM能够加速AMI后心肌重塑的进展。基因芯片分析显示随着时间的变化,两组大鼠基因表达显著不同,糖尿病大鼠AMI后左心室非梗死区心肌组织有1221个基因表达与非糖尿病大鼠显著不同,其中770个表达上调,451个表达下调;对差异基因进行功能分析发现其涵盖糖代谢、脂肪酸代谢、细胞外基质、凋亡、氧化还原和磷酸酶活性等诸多方面。无监督聚类分析发现糖尿病大鼠AMI后左心室非梗死区1-7天的基因表达变化和非糖尿病大鼠相似,14天时的基因表达变化与非糖尿病大鼠14和28天相似,而其28和56天的基因变化和非糖尿病大鼠56天相似,显示糖尿病大鼠AMI后重塑相关基因的表达谱提前1-2周。根据筛选条件,应用到无监督聚类分析的基因为164个,其中118个已经被命名,大部分被证实与心脏重构密切相关,例如富含亮氨酸的PPR模体(白介素-6信号通路)、原骨胶原Ⅰ型和Ⅲ型、纤维连接蛋白1、RT1,and TIMP-1等等。
结论:STZ诱导的1型糖尿病大鼠急性心肌梗死后心功能的恶化可能与相关基因表达谱的前移和过量表达有关。
目的:观察糖尿病大鼠AMI后梗死周边区的心肌细胞凋亡的时间依赖性变化。
方法:SD大鼠应用STZ一次性腹腔注射(65mg/dl)诱导1型糖尿病10周,未进行降糖治疗;结扎冠状动脉前降支,取材,应用免疫细胞化学Tunel法检测细胞凋亡。取材左心室梗死周边区组织(距离心肌梗死边缘2.5mm范围),应用免疫印迹(Western blot)法半定量分析凋亡相关蛋白Bax和Bcl-2蛋白水平的含量;应用实时定量PCR(real time-PCR)法定量分析结缔组织生长因子(CTGF)和caspase-3mRNA水平的表达。
结果:研究显示STZ诱导10周后,糖尿病大鼠心肌组织凋亡指数显著高于非糖尿病大鼠(3.2±0.5 vs.1.4±0.3,P＜0.01);在急性心肌梗死后的1天(20.1±1.8 vs.16.9±1.5,P＜0.05)、7天(16.1±1.7 vs.12.9±1.3,P＜0.01)、14天(16.1±1.7 vs.13.1±1.4,P＜0.05)、28天(15.2±1.8 vs.11.9±1.5,P＜0.01]和56天(16.3±1.6 vs.9.6±1.2,P＜0.001)时其左心室梗死周边区心肌细胞进行性凋亡,凋亡指数(括号中数值)显著高于非糖尿病大鼠。和非糖尿病组大鼠相比,Western blot法半定量分析显示糖尿病大鼠急性心肌梗死后1天、7天、28天和56天促凋亡蛋白Bax水平显著增加(P＜0.001);而抑凋亡蛋白Bcl-2水平在AMI后1天、14天、28天和56天显著降低(P＜0.001)。实时定量PCR结果显示CTGF和caspase-3mRNA的水平较非糖尿病大鼠显著增加。
结论:与非糖尿病大鼠相比,糖尿病大鼠急性心肌梗死后左心室梗死周边区的细胞进行性凋亡可能会导致其左心室扩大和心肌纤维化的程度显著较高,从而更加容易发生心力衰竭;其Bax和Bcl-2的蛋白水平提示其细胞凋亡通路可能包含线粒体凋亡通路。
Objective:In spite of numerous studies in diabetic animal models,to our knowledge,myocardial performance,especially time course study was never performed in untreated diabetic myocardial infarction(MI) rat model without reperfusion.
Methods:In the present study,myocardial function and structure changes of myocardium were examined in untreated streptozotocin(STZ)-induced diabetic MI rat model without perfusion. DM was induced with a single intraperitoneal injection of STZ(65 mg/kg),and body weight was recorded and serum glucose levels were determined at baseline,day 3,day 7,day 30 and day 70 after STZ injection by using One Touch Sure Step test strips and meter(Life Scan,Johnson & Johnson,Warren NJ,USA).Ten weeks after DM induction without any therapy,the left anterior descending coronary artery of diabetic Sprague-Dawley rats was ligated to induce no-reperfusion MI model Tissue structure of myocardium,two-dimensional echocardiography,and hemodynamic studies were utilized to monitor the time course changes of above relating parameters up to 56 days.
Results:Ten weeks after DM established,serum glucose levels were significantly higher in the diabetic rats(489±28mg/dl) than in the non-diabetic animals(112±13mg/dl,P＜0.001).Body weights were significantly lower in the diabetic rats(244.8±23.6g) than that of non-diabetic ones (516.3±48.6g,P＜0.001).TEM examination showed that the heart of diabetic rats contained increased lipid droplets and glycogen particles around mitochondria and scattered mitochondrial damage(swelling and disrupted cristae);in addition,cardiac muscle fibers were identified to be crumbly in the majority of the diabetic rats,and the basal lamina of regional small vessels was thicker in some regions.After AMI,Diabetic rats experienced lower survival rate in both acute phase(1,7 and 14 days) and chronic phase(28 and 56 days) compared with non-diabetic rats at corresponding time points.During 56 days after myocardial infarction,worse left ventricular function(EF 37.3±5.4 vs.48.8±4.1,P＜0.01 and FS 17.0±1.4 vs.23.7±2.5,P＜0.05) and larger the left ventricular diameter(increased LVEDD 47.5±5.2%vs.26.8±4.9%,P＜0.001) were identified in diabetic rats than in non-diabetics.Furthermore,diabetic rats showed more serious myocardial fibrosis by quantification of fibrosis area in the remote zone of left ventricular free wall compared with non-diabetic ones at 28 and 56 days after MI(Masson's quantitation 10.3%±1.5%vs.3.8%±0.9%,P＜0.001 and 17.5%±2.1%vs.9.8%±1.2%,P＜0.001).
Conclusion:The different patterns of the pathophysiologic changes in the untreated STZ-induced diabetic MI rat model without reperfusion might suggest that in the early phase after AMI,LV diastolic dysfunction may account for the higher incidence of HF and death,while in the prolonged phase,both LV dysfunction and accelerated cardiac remodeling can be the motivation.
Objective:To study the time-dependent effects of genetic changes in untreated Streptozotocin (STZ)-induced diabetic rat with MI.
Methods:The left anterior descending coronary arteries were ligated 10 weeks after DM induction without any therapy and reperfusion.Microarray analysis and real time-PCR were utilized to monitor the time-dependent genetic changes in the remote zone of LV up to 56 days.
Results:The gene expression related to cardiac remodeling in the remote zone was quite different as time elapses between both groups.Total 1221 genes were found to be differentially expressed between diabetics and non-diabetics,770 unregulated and 451 downregulated, involving in glucose metabolism,fatty acid metabolism,extracellular matrix,apoptosis, oxido-reductase activity,phosphoprotein phosphatase activity,etc.The gene expression at 1 and 7 days post acute MI in diabetic and non-diabetic group was similar,while such changes at day 14 in diabetic rats were comparable to both 14 and 28 days in non-diabetic rats;moreover,the pattern of gene expression at day 28 and 56 in diabetic rats was similar to the ones at day 56 in non-diabetic rats,which may indicate that upregulation of the genes was found one-two weeks earlier in diabetic rats than in non-diabetic rats.In primary examination,164 genes(118 named) were found to be candidates for hierarchical analysis,such as leucine-rich PPR-motif containing (interleukin-6 signaling pathway),procollagen typeⅠandⅢ,fibronectin-1,RT1,and TIMP-1,etc.
Conclusion:The present data support that diabetes upregulates remodeling-related gene,which may be responsible for the worse outcomes in diabetes than in non-diabetes after myocardial infarction.
Objective:To examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.
Methods:Ten weeks after intravenous streptozotocin(diabetic groups) or citrate buffer(controls) injection,myocardial infarction was produced by ligation of left descending coronary artery.Level of cardiomyocyte apoptosis was quantified by TUNEL method;Bax and Bcl-2 proteins were determined by western blot method;CTGF and caspase-3 were quantitated by real time-PCR.
Results:The number of apoptotic cardiomyocytes was higher in diabetic than in non-diabetic rats after 10 weeks of DM induction(apototic index,3.2±0.5 vs.1.4±0.3,P<0.01).At 1d(20.1±1.8 vs.16.9±1.5,P<0.05),7d(16.1±1.7 vs.12.9±1.3,P<0.01),14d(16.1±1.7 vs.13.1±1.4,P<0.05), 28d(15.2±1.8 vs.11.9±1.5,P<0.01) and 56d(16.3±1.6 vs.9.6±1.2,P<0.001) after myocardial infarction,the apoptotic indices in the border zone of infarction area was higher in the diabetic as compared to non-diabetic rats.Correspondingly,Bax,connective tissue growth factor and caspase-3 expression were increased in diabetic compared with non-diabetic rats with myocardial infarction,whereas Bcl-2 expression was decreased.
Conclusion:Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.
引文
[1].中华医学会分会心血管病学会.慢性心力衰竭的治疗建议.中会心血管病杂志.2002;30:7-23.
[2].Dickstein K,Cohen-Solal A,Filippatos G,McMurray JJ,Ponikowski P,Poole-Wilson PA,Stromberg A,van Veldhuisen DJ,Atar D,Hoes AW,Keren A,Mebazaa A, Nieminen M,Priori SG,Swedberg K,Vahanian A,Camm J,De Caterina R,Dean V,Funck-Brentano C,Hellemans I,Kristensen SD,McGregor K,Sechtem U,Silber S,Tendera M,Widimsky P,Zamorano JL,Auricchio A,Bax J,Bohm M,Corra U,della Bella P,Elliott PM,Follath F,Gheorghiade M,Hasin Y,Hernborg A,Jaarsma T,Komajda M,Kornowski R,Piepoli M,Prendergast B,Tavazzi L,Vachiery JL,Verheugt FW,Zannad F.ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology.Developed in collaboration with the Heart Failure Association of the ESC(HFA)and endorsed by the European Society of Intensive Care Medicine(ESICM).Eur J Heart Fail.2008;10(10):933-989.
[3].Haffner SM,Lehto S,Ronnemaa T,Pyorala K,Laakso M.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.The New England journal of medicine.1998;339(4):229-234.
[4].Carrabba N,Valenti R,Parodi G,Santoro GM,Antoniucci D.Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation.2004;110(14):1974-1979.
[5].Norhammar A,Tenerz A,Nilsson G,Hamsten A,Efendic S,Ryden L,Malmberg K.Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus:a prospective study.Lancet.2002;359(9324):2140-2144.
[6].Greer JJ,Ware DP,Lefer DJ.Myocardial infarction and heart failure in the db/db diabetic mouse.Am J Physiol Heart Circ Physiol.2006;290(1):H146-153.
[7].Wencker D,Chandra M,Nguyen K,Miao W,Garantziotis S,Factor SM,Shirani J,Armstrong RC,Kitsis RN.A mechanistic role for cardiac myocyte apoptosis in heart failure.J Clin Invest.2003;111(10):1497-1504.
[8].Backlund T,Palojoki E,Saraste A,Eriksson A,Finckenberg P,Kyto V,Lakkisto P,Mervaala E,Voipio-Pulkki LM,Laine M,Tikkanen I.Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.Diabetologia.2004;47(2):325-330.
[9].Yoon YS,Uchida S,Masuo O,Cejna M,Park JS,Gwon HC,Kirchmair R,Bahlman F,Walter D,Curry C,Hanley A,Isner JM,Losordo DW.Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy:restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.Circulation.2005;111(16):2073-2085.
[10].Chandler MP,Morgan EE,McElfresh TA,KungTA,Rennison JH,Hoit BD,Young ME.Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats.Am J Physiol Heart Circ Physiol.2007;293(3):H 1609-1616.
[11].Popper SJ,Shimizu C,Shike H,Kanegaye JT,Newburger JW,Sundel RP,Brown PO,Burns JC,Relman DA.Gene-expression patterns reveal underlying biological processes in Kawasaki disease.Genome Biol.2007;8(12):R261.
[12].Flamez D,Berger V,Kruhoffer M,Orntoft T,Pipeleers D,Schuit FC.Critical role for cataplerosis via citrate in glucose-regulated insulin release.Diabetes.2002;51(7):2018-2024.
[13].Warnat P,Oberthuer A,Fischer M,Westermann F,Eils R,Brors B.Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes.BMC Cancer.2007;7:89.
[14].Feuvray D,Idell-Wenger JA,Neely JR.Effects of ischemia on rat myocardial function and metabolism in diabetes.Circulation research.1979;44(3):322-329.
[15].Lopaschuk GD,Spafford M.Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats.Circulation research.1989;65(2):378-387.
[16].Tani M,Neely JR.Hearts from diabetic rats are more resistant to in vitro ischemia:possible role of altered Ca2+ metabolism.Circulation research.1988;62(5):931-940.
[17].Khandoudi N,Bernard M,Cozzone P,Feuvray D.Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts.Cardiovascular research.1990;24(11):873-878.
[18].Khandoudi N,Bernard M,Cozzone P,Feuvray D.Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts.Diabetes.1995;44(2):196-202.
[19].Paulson DJ,Kopp SJ,Peace DG,Tow JP.Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats.J Appl Physiol.1988;65(1):187-193.
[20].Paulson DJ,Shug AL,Zhao J.Protection of the ischemic diabetic heart by L-propionylcarnitine therapy.Mol Cell Biochem.1992;116(1-2):131-137.
[21].Hsueh W,Abel ED,Breslow JL,Maeda N,Davis RC,Fisher EA,Dansky H,McClain DA,Mclndoe R,Wassef MK,Rabadan-Diehl C,Goldberg IJ.Recipes for creating animal models of diabetic cardiovascular disease.Circulation research. 2007;100(10):1415-1427.
[22].Pfeffer JM,Pfeffer MA,Braunwald E.Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure.Circulation.1987;75(1 Pt 2):I149-155.
[23].Litwin SE,Katz SE,Morgan JP,Douglas PS.Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat.Circulation.1994;89(1):345-354.
[24].Semeniuk LM,Kryski AJ,Severson DL Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.Am J Physiol Heart Circ Physiol.2002;283(3):H976-982.
[25].Paulson DJ.The diabetic heart is more sensitive to ischemic injury.Cardiovascular research.1997;34(1):104-112.
[26].Wohaieb SA,Godin DV.Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat.Effects of insulin treatment.Diabetes.1987;36(9):1014-1018.
[27].Tosaki A,Engelman DT,Engelman RM,Das DK.The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research.1996;31(4):526-536.
[28].Paulson DJ,Schmidt MJ,Romens J,Shug AL Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia:effects of L-acetylcarnitine.Basic Res Cardiol.1984;79(5):551-561.
[29].Higuchi M,Ikema S,Matsuzaki T,Hirayama K,Sakanashi M.Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts(?)solated from normal and diabetic rats.Journal of molecular ana(?)cellular cardiology.1991;23(2)(?)137-148.
[30].De Groote P,Lam(?)llin N,Mouquet F,Plichon D,Mc(?)adden E,Van Belle E,Bauters C.Impact of diabetes mellitus on long-term survival in patients with congestive heart failure.European heart journal.2004;25(8):656-662.
[31].McGuire DK,Newby LK,Bhapkar MV,Moliterno DJ,Hochman JS,Klein WW,Weaver WD,Pfisterer M,Corbalan R,Dellborg M,Granger CB,Van De Werf F,Topol EJ,Califf RM.Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.Am Heart J.2004;147(2):246-252.
[32].Jagasia D,McNulty PH.Diabetes mellitus and heart failure.Congest Heart Fail.2003;9(3):133-139;quiz 140-131.
[33].Raev DC.Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy?An echocardiographic study of young type I diabetic patients.Diabetes care.1994;17(7):633-639.
[34].Borges GR,de Oliveira M,Salgado HC,Fazan R,Jr.Myocardial performance in conscious streptozotocin diabetic rats.Cardiovascular diabetology.2006;5:26.
[35].Solomon SD,St John Sutton M,Lamas GA,Plappert T,Rouleau JL,Skali H,Moye L,Braunwald E,Pfeffer MA.Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.Circulation.2002;106(10):1251-1255.
[36].Yue P,Long CS,Austin R,Chang KC,Simpson PC,Massie BM.Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype.Journal of molecular and cellular cardiology.1998;30(8):1615-1630.
[37].Ono K,Matsumori A,Shioi T,Furukawa Y,Sasayama S.Cytokine gene expression after myocardial infarction in rat hearts:possible implication in left ventricular remodeling.Circulation.1998;98(2):149-156.
[38].Stanton LW,Garrard U,Damm D,Garrick BL,Lam A,Kapoun AM,Zheng Q,Protter AA,Schreiner GF,White RT.Altered patterns of gene expression in response to myocardial infarction.Circulation research.2000;86(9):939-945.
[39].Panes J,Kurose I,Rodriguez-Vaca D,Anderson DC,Miyasaka M,Tso P,Granger DN.Diabetes exacerbates inflammatory responses to ischemia-reperfusion.Circulation.1996;93(1):161-167.
[40].Xiao XH,Allen DG.Role of Na(+)/H(+)exchanger during ischemia and preconditioning in the isolated rat heart.Circulation research.1999;85(8):723-730.
[41].Ramasamy R,Schaefer S.Inhibition of Na+-H+ exchanger protects diabetic and non-diabetic hearts from ischemic injury:insight into altered susceptibility of diabetic hearts to ischemic injury.Journal of molecular and cellular cardiology.1999;31(4):785-797.
[42].Lagadic-Gossmann D,Buckler KJ,Le Prigent K,Feuvray D.Altered Ca2+handling in ventricular myocytes isolated from diabetic rats.The American journal of physiology.1996;270(5 Pt 2):H 1529-1537.
[43],Forrat R,Sebbag L,Wiernsperger N,Guidollet J,Renaud S,de Lorgeril M.Acute myocardial infarction in dogs with experimental diabetes.Cardiovascular research.1993;27(11):1908-1912.
[44].Ravingerova T,Neckar J,Kolar F.Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes.Molecular and cellular biochemistry.2003;249(1-2):167-174.
[45].Macgregor S,Zhao ZZ,Henders A,Nicholas MG,Montgomery GW,Visscher PM.Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays.Nucleic Acids Res.2008;36(6):e35.
[46].Bar-Joseph Z,Gifford DK,Jaakkola TS.Fast optimal leaf ordering for hierarchical clustering.Bioinformatics.2001;17 Suppl 1:S22-29.
[47].Liu H,Tarima S,Borders AS,Getchell TV,Getchell ML,Stromberg AJ.Quadratic regression analysis for gene discovery and pattern recognition for non-cyclic short time-course microarray experiments.BMC Bioinformatics.2005;6:106.
[48].Hosack DA,Dennis G,Jr.,Sherman BT,Lane HC,Lempicki RA.Identifying biological themes within lists of genes with EASE.Genome Biol.2003;4(10):R70.
[49].Tyagi SC,Rodriguez W,Patel AM,Roberts AM,Falcone JC,Passmore JC,Fleming JT,Joshua IG.Hyperhomocysteinemic diabetic cardiomyopathy:oxidative stress,remodeling,and endothelial-myocyte uncoupling.Journal of cardiovascular pharmacology and therapeutics.2005;10(1):1-10.
[50].Suleiman M,Aronson D,Asleh R,Kapeliovich MR,Roguin A,Meisel SR,Shochat M,Sulieman A,Reisner SA,Markiewicz W,Hammerman H,Lotan R,Levy NS,Levy AP.Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction.Diabetes.2005;54(9):2802-2806.
[51].Belke DD,Larsen TS,Gibbs EM,Severson DL.Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic(db/db)mice.Am J Physiol Endocrinol Metab.2000;279(5):E1104-1113.
[52].Chatham JC,Seymour AM.Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.Cardiovascular research.2002;55(1):104-112.
[53].An D,Rodrigues B.Role of changes in cardiac metabolism in development of diabetic cardiomyopathy.Am J Physiol Heart Circ Physiol.2006;291(4):H1489-1506.
[54].Smith HM,Hamblin M,Hill MF.Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure.Journal of molecular and cellular cardiology.2005;39(4):657-665.
[55].Cai L,Wang J,Li Y,Sun X,Wang L,Zhou Z,Kang YJ.Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy.Diabetes.2005;54(6):1829-1837.
[56].Nystrom T,Nygren A,Sjoholm A.Increased levels of tumour necrosis factor-alpha(TNF-alpha)in patients with Type Ⅱ diabetes mellitus after myocardial infarction are related to endothelial dysfunction.Clin Sci(Lond).2006;110(6):673-681.
[57].Giacchetti G,Sechi LA,Rilli S,Carey RM.The renin-angiotensin-aldosterone system,glucose metabolism and diabetes.Trends Endocrinol Metab.2005;16(3):120-126.
[58].Di Filippo C,Marfella R,Cuzzocrea S,Piegari E,Petronella P,Giugliano D,Rossi F,D'Amico M.Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.Diabetes.2005;54(3):803-810.
[59].Xu YJ,Chapman D,Dixon IM,Sethi R,Guo X,Dhalla NS.Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation.Journal of cellular and molecular medicine.2004;8(1):85-92.
[60].Pfeffer JM,Pfeffer MA,Fletcher PJ,Braunwald E.Progressive ventricular remodeling in rat with myocardial infarction.The American journal of physiology.1991;260(5 Pt 2):H1406-1414.
[61].Maisch B.Ventricular remodeling.Cardiology.1996;87 Suppl 1:2-10.
[62].Howard BV,Wylie-Rosett J.Sugar and cardiovascular disease:A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition,Physical Activity,and Metabolism of the American Heart Association.Circulation.2002;106(4):523-527.
[63].Cai L,Li W,Wang G,Guo L,Jiang Y,Kang YJ.Hyperglycemia-induced apoptosis in mouse myocardium:mitochondrial cytochrome C-mediated caspase-3 activation pathway.Diabetes.2002;51(6):1938-1948.
[64].Spierings D,McStay G,Saleh M,Bender C,Chipuk J,Maurer U,Green DR.Connected to death:the(unexpurgated)mitochondrial pathway of apoptosis.Science.2005;310(5745):66-67.
[65].Shiomi T,Tsutsui H,Ikeuchi M,Matsusaka H,Hayashidani S,Suematsu N,Wen J,Kubota T,Takeshita A.Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction.Journal of the American College of Cardiology.2003;42(1):165-172.
[66].Abbate A,Biondi-Zoccai GG,Baldi A.Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodeling.J Cell Physiol.2002;193(2):145-153.
[67].Zhang H,Li Q,Li Z,Mei Y,Guo Y.The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by analogous ischemia/reperfusion in vitro.Neurosci Res.2008;62(2):140-146.
[68].Chen N,Deng T,Chen P,Li L.[The regulation of apoptosis by Bcl-2,bcl-X(L),Bcl-2alpha and Bax in chronic liver disease].Zhonghua Nei Ke Za Zhi. 2000;39(12):808-810.
[69].Wong WW,Puthalakath H.Bcl-2 family proteins:the sentinels of the mitochondrial apoptosis pathway.IUBMB life.2008;60(6):390-397.
[70].Hishikawa K,Oemar BS,Nakaki T.Static pressure regulates connective tissue growth factor expression in human mesangial cells.J Biol Chem.2001;276(20):16797-16803.
[71].Way KJ,Isshiki K,Suzuma K,Yokota T,Zvagelsky D,Schoen FJ,Sandusky GE,Pechous PA,Vlahos CJ,Wakasaki H,King GL.Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2activation and diabetes.Diatbetes.2002;51(9):2709-2718.
[1]Diamant M,Lamb HJ,Groeneveld Y,et al.Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus.Journal of the American College of Cardiology 2003;42:328-35.
[2]Taegtmeyer H,McNulty P,Young ME.Adaptation and mahdaptation of the heart in diabetes:Part Ⅰ:general concepts.Circulation 2002;105:1727-33.
[3]Hayat SA,Patel B,Khattar RS,et at Diabetic cardiomyopathy:mechanisms,diagnosis and treatmnent.Clin Sci(Lond) 2004;107:539-57.
[4]Jagasia D,McNulty PH.Diabetes mellitus and heart failure.Congest Heart Fail 2003;9:133-9;quiz 40-1.
[5]Carrabba N,Valenti R,Parodi G,et at Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation 2004;110:1974-9.
[6]Haffner SM,Lehto S,Ronnemaa T,et al.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.The New England journal of medicine 1998;339:229-34.
[7]Janghorbani M,Hu FB,Willett WC,et al.Prospective study of type 1 and type 2diabetes and risk of stroke subtypes:the Nurses' Health Study.Diabetes care 2007;30:1730-5.
[8]Grundy SM,Cleeman JI,Merz CN,et al.Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel Ⅲ guidelines.Circulation 2004;110:227-39.
[9]Norhammar A,Tenerz A,Nilsson G,et al.Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus:a prospective study.Lancet 2002;:359:2140-4.
[10]Miettinen H,Lehto S,Salomaa V,et at Impact of diabetes on mortality after the first myocardial infarction.The FINMONICA Myocardial Infarction Register Study Group.Diabetes care 1998;21:69-75.
[11]McGuire DK,Newby LK,Bhapkar MV,et at Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.American heart journal 2004;147:246-52.
[12]Wagner AM,Martijnez-Rubio A,Ordonez-Llanos J,et al.Diabetes mellitus and cardiovascular disease.Eur J Intern Med 2002;13:15-30.
[13]Paulson DJ.The diabetic heart is more sensitive to ischemic injury.Cardiovascular research 1997;34:104-12.
[14]Feuvray D,Lopaschuk GD.Controversies on the sensitivity of the diabetic heart to ischemic injury:the sensitivity of the diabetic heart to ischemic injury is decreased.Cardiovascular research 1997;34:113-20.
[15]Lopaschuk GD,Spafford M.Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats.Circulation research 1989;65:378-87.
[16]Paulson DJ,Kopp SJ,Peace DG,et aL Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats.J Appl Physiol 1988;65:187-93.
[17]Paulson DJ,Shug AL,Zhao J.Protection of the ischemic diabetic heart by L-propionylcarnitine therapy.Mol Cell Biochem 1992;116:131-7.
[18]Khandoudi N,Bernard M,Cozzone P,et aL Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts.Cardiovascular research 1990;24:873-8.
[19]Wohaieb SA,Godin DV.Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat.Effects of insulin treatment.Diabetes 1987;36:1014-8.
[20]Tosaki A,Engelman DT,Engelman RM,et aL The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research 1996;31:526-36.
[21]Paulson DJ,Schmidt MJ,Romens J,et aL Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia:effects of L-acetylcarnitine.Basic Res Cardiol 1984;79:551-61.
[22]Higuchi M,Ikema S,Matsuzaki T,et aL Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts isolated from normal and diabetic rats.Journal of molecular and cellular cardiology 1991;23:137-48.
[23]Capes SE,Hunt D,Malmberg K,et aL Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes:a systematic overview.Lancet 2000;355:773-8.
[24]Oswald GA,Corcoran S,Yudkin JS.Prevalence and risks of hyperglycaemia and undiagnosed diabetes in patients with acute myocardial infarction.Lancet 1984;1:1264-7.
[25]Kosiborod M,Rathore SS,Inzucchi SE,et al.Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction:implications for patients with and without recognized diabetes.Circulation 2005;111:3078-86.
[26]Meier JJ,Deifuss S,Khmann A,et al.Phsma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes:the Langendreer Myocardial Infarction and Blood Glucose in Diabetic Patients Assessment(LAMBDA).Diabetes care 2005;28:25.51-3.
[27]L L,Van den Berghe G.Glucose metabolism and insulin therapy.Crit Care Clin 2006;22:119-29,ⅶ.
[28]Malmberg K.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus.DIGAMI(Diabetes Mellitus,Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.BMJ 1997;314:1512-5.
[29]Deedwania P,Kosiborod M,Barrett E,et al.Hyperglycemia and acute coronary syndrome:a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition,Physical Activity,and Metabolism.Anesthesiology 2008;109:14-24.
[30]Esposito K,Nappo F,Marfella R,et al.Inflammatory.cytokine concentrations are acutely increased by hyperglycemia in humans:role of oxidative stress.Circulation 2002;106:2067-72.
[31]Haber CA,Lam TK,Yu Z,et al.N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo:possible role of oxidative stress.Am J Physiol Endocrinol Metab 2003;285:E744-53.
[32]Suleiman M,Hammerman H,Boulos M,et al.Fasting glucose is an important independent risk factor for 30-day mortality in patients with acute myocardial infarction:a prospective study.Circulation.2005;111:754-60.
[33]中国心脏调查组.中国住院冠心病患者糖代谢异常研究-中国心脏调查.中华内分泌杂志 2006;22:7-10.
[34]Hadjadj S,Coisne D,Mauco G,et al.Prognostic value of admission plasma glucose and HbA in acute myocardial infarction.Diabet Med 2004;21:305-10.
[35]Ryden L,Standl E,Bartnik M,et al.Guidelines on diabetes,pre-diabetes,and cardiovascular diseases:executive summary.The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology(ESC) and of the European Association for the Study of Diabetes(EASD).European heart journal 2007;28:88-136.
[36]van den Berghe G,Wouters P,Weekers F,et al.Intensive insulin therapy in the critically ill patients.The New England journal of medicine 2001;345:1359-67.
[37]Malmberg K,Ryden L,Wedel H,et al.Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction(DIGAMI 2):effects on mortality and morbidity.European heart journal 2005;26:650-61.
[1]Song GY,Wu YJ,Yang YJ,et al.Diabetes mellitus can accerate the progression of post-infarction genetic regulatory expression in untreated Streptozotocin-induced Diabetic Rat Model.ESC Acute Cardiac Care Abstract 2008.
[2]Tosaki A,Engelman DT,Engelman RM,et al.The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research 1996;31:526-36.
[3]Semeniuk LM,Kryski AJ,Severson DL.Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.Am J Physiol Heart Circ Physiol 2002;283:H976-82.
[4]Rajan SK,Gokhale SM.Cardiovascular function in patients with insulin-dependent diabetes mellitus:a study using noninvasive methods.Ann N Y Acad Sci 2002;958:425-30.
[5]Joffe,Ⅱ,Travers KE,Perreault-Micale CL,et al Abnormal cardiac function in the streptozotocin-induced non-insulin-dependent diabetic rat:noninvasive assessment with doppler echocardiography and contribution of the nitric oxide pathway.Journal of the American College of Cardiology 1999;34:2111-9.
[6]Trost SU,Belke DD,Bluhm WF,et al.Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in diabetic cardiomyopathy.Diabetes 2002;51:1166-71.
[7]Poirier P,Bogaty P,Garneau C,et al.Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes:importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy.Diabetes care 2001;24:5-10.
[8]Schannwell CM,Schneppenheim M,Perings S,et al.Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy.Cardiology 2002;98:33-9.
[9]Friedman NE,Levitsky LL,Edidin DV,et aL Echocardiographic evidence for impaired myocardial performance in children with type I diabetes mellitus.Am J Med 1982;73:846-50.
[10]Mizushige K,Yao L,Noma T,et al.Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type Ⅱ diabetic rat model.Circulation 2000;101:899-907.
[11]Cai L,Wang J,Li Y,et aL Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy.Diabetes 2005;54:1829-37.
[12]Regan TJ,Lyons MM,Ahmed SS,et aL Evidence for cardiomyopathy in familial diabetes mellitus.J Clin Invest 1977;60:884-99.
[13]Nunoda S,Genda A,Sugihara N,et al.Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus.Heart Vessels 1985;1:43-7.
[14]Vitolo E,Madoi S,Sponzilli C,et al.Vectorcardiographic evaluation of diabetic cardiomyopathy and of its contributing factors.Acta Diabetol hat 1988;25:227-34.
[15]Fang ZY,Yuda S,Anderson V,et al.Echocardiographic detection of early diabetic myocardial disease.Journal of the American College of Cardiology 2003;41:611-7.
[16]Chatham JC,Seymour AM.Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.Cardiovascular research 2002;55:104-12.
[17]Garvey WT,Hardin D,Juhaszova M,et aL Effects of diabetes on myocardial glucose transport system in rats:implications for diabetic cardiomyopathy.The American journal of physiology 1993;264:H837-44.
[18]Nakayama H,Morozumi X Nanto S,et aL Abnormal myocardial free fatty acid utilization deteriorates with morphological changes in the hypertensive heart.Jpn CircJ 2001;65:783-7.
[19]Malhotra A,Sanghi V.Regulation of contractile proteins in diabetic heart.Cardiovascular research 1997;34:34-40.
[20]Dhalla NS,Liu X,Panagia V,et aL Subcellular remodeling and heart dysfunction in chronic diabetes.Cardiovascular research 1998;40:239-47.
[21]Abe X Ohga Y,Tabayashi N,et al.Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats.Am J Physiol Heart Circ Physiol 2002;282:H138-48.
[22]Yoon YS,Uchida S,Masuo O,et aL Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy:restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.Circulation 2005;111:2073-85.
[23]Haunstetter A,Izumo S.Apoptosis:basic mechanisms and implications for cardiovascular disease.Circulation research 1998;82:1111-29.
[24]Li B,Setoguchi M,Wang X,et aL Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart.Circulation research 1999;84:1007-19.
[25]Fiordaliso F,Leri A,Cesselli D,et aL Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death.Diabetes 2001;50:2363-75.
[26]Chen S,Evans T,Mukherjee K,et aL Diabetes-induced myocardial structural changes:role of endothelin-1 and its receptors.Journal of molecuhr and cellular cardiology 2000;32:1621-9.
[27]Cai L,Li W,Wang G,et aL Hyperglycemia-induced apoptosis in mouse myocardium:mitochondrial cytochrome C-mediated caspase-3 activation pathway.Diabetes 2002;51:1938-48.
[28]Kajstura J,Fiordaliso F,Andreoli AM,et aL IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin Ⅱ-mediated oxidative stress.Diabetes 2001;50:1414-24.
[29]Hayat SA,Patel B,Khattar RS,et aL Diabetic cardiomyopathy:mechanisms,diagnosis and treatment.Clin Sci(Lond)2004;107:539-57.
[30]Nitenberg A,Valensi P,Sachs R,et al.Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.Diabetes 1993;42:1017-25.
[31]Meyer C,Schwaiger M.Myocardial blood flow and glucose metabolism in diabetes mellitus.The American journal of cardiology 1997;80:94A-101A.
[32]Johnstone MT,Creager SJ,Scales KM,et aL Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.Circulation 1993;88:2510-6.
[33]Taylor PD,Graves JE,Poston L.Selective impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated resistance arteries of the streptozotocin-induced diabetic rat.Clin Sci(Lond)1995;88:519-24.
[34]Bucala R,Tracey KJ,Cerami A.Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.J Clin Invest 1991;87:432-8.
[35]Rosen P,Ballhausen T,Bloch W,et aL Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart influence of tocopherol as antioxidant.Diabetologia 1995;38:1157-68.
[36]Tesfamariam B,Jakubowski JA,Cohen RA.Contraction of diabetic rabbit aorta caused by endothelium-derived PGH2-TxA2.The American journal of physiology 1989;257:H1327-33.
[37]Koya D,King GL.Protein kinase C activation and the development of diabetic complications.Diabetes 1998;47:859-66.
[38]Fernandez-Real JM,Lainez B,Vendrell J,et aL Shedding of TNF-alpha receptors,btood pressure,and insulin sensitivity in type 2 diabetes mellitus.Am J Physiol Endocrinol Metab 2002;282:E952-9.
[39]Quilliot D,Fluckiger L,Zannad F,et aL Impaired autonomic control of heart rate and blood pressure in obesity:role of age and of insulin-resistance.Clin Auton Res 2001;11:79-86.
[40]de Kreutzenberg SV,Avogaro A,Tiengo A,et aL Left ventricular mass in type 2 diabetes mellitus.A study employing a simple ECG index:the Cornell voltage.J Endocrinol Invest 2000;23:139-44.
[41]Hirayama H,Sugano M,Abe N,et aL Troglitazone,an antidiabetic drug,improves left ventricular mass and diastolic function in normotensive diabetic patients.Int J Cardiol 2001;77:75-9.
[42]Hintz KK,Ren J.Prediabetic insulin resistance is not permissive to the development of cardiac resistance to insulin-like growth factor I in ventricular myocytes.Diabetes Res Clin Pract 2002;55:89-98.
[43]Rutter MK,Parise H,Benjamin EJ,et aL Impact of glucose intolerance and insulin resistance on cardiac structure and function:sex-related differences in the Framingham Heart Study.Circulation 2003;107:448-54.
[44]Estep JD,Aguilar D.Diabetes and heart failure in the post-myocardial infarction patient.Curr Heart Fail Rep 2006;3:164-9.
[45]Aguilar D,Solomon SD,Kober L,et aL Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction:the VALsartan In Acute myocardial iNfarcTion(VALIANT)triaL Circulation 2004;110:1572-8.
[46]Murcia AM,Hennekens CH,Lamas GA,et aL Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction.Arch Intern Med 2004;164:2273-9.
[47]Mak KH,Moliterno DJ,Granger CB,et al.Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction.GUSTO-I Investigators.Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.Journal of the American College of Cardiology 1997;30:171-9.
[48]Woodfield SL,Lundergan CF,Reiner JS,et al.Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction:the GUSTO-I experience.Journal of the American College of Cardiology 1996;28:1661-9.
[49]Prasad A,Stone GW,Stuckey TD,et al.Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction.Journal of the American College of Cardiology 2005;45:508-14.
[50]Solomon SD,St John Sutton M,Lamas GA,et al.Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.Circulation 2002;106:1251-5.
[51]Carrabba N,Valenti R,Parodi G,et al.Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation 2004;110:1974-9.
[52]Chandler MP,Morgan EE,McElfresh TA,et al.Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats.Am J Physiol Heart Circ Physiol 2007;293:H1609-16.
[53]Suleiman M,Aronson D,Asleh R,et al.Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction.Diabetes 2005;54:2802-6.
[54]An D,Rodrigues B.Role of changes in cardiac metabolism in devetopment of diabetic cardiomyopathy.Am J Physiol Heart Circ Physiol 2006;291:H1489-506.
[55]Nystrom T,Nygren A,Sjoholm A.Increased levels of tumour necrosis factor-alpha(TNF-alpha)in patients with Type Ⅱ diabetes mellitus after myocardial infarction are related to endothelial dysfunction.Clin Sci(Lond)2006;110:673-81.
[56]Giacchetti G,Sechi LA,Rilli S,et al.The renin-angiotensin-aldosterone system,glucose metabolism and diabetes.Trends Endocrinol Metab 2005;16:120-6.
[57]Backlund T,Palojoki E,Saraste A,et al.Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.Diabetologia 2004;47:325-30.
[58]Tyagi SC,Rodriguez W,Patel AM,et al.Hyperhomocysteinemic diabetic cardiomyopathy:oxidative stress,remodeling,and endothelial-myocyte uncoupling.Journal of cardiovascular pharmacology and therapeutics 2005;10:1-10.
[59]Smith HM,Hamblin M,Hill MF.Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure.Journal of molecular and cellular cardiology 2005;39:657-65.
[60]Di Filippo C,Marfella R,Cuzzocrea S,et al.Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.Diabetes 2005;54:803-10.
[2].Dickstein K,Cohen-Solal A,Filippatos G,McMurray JJ,Ponikowski P,Poole-Wilson PA,Stromberg A,van Veldhuisen DJ,Atar D,Hoes AW,Keren A,Mebazaa A, Nieminen M,Priori SG,Swedberg K,Vahanian A,Camm J,De Caterina R,Dean V,Funck-Brentano C,Hellemans I,Kristensen SD,McGregor K,Sechtem U,Silber S,Tendera M,Widimsky P,Zamorano JL,Auricchio A,Bax J,Bohm M,Corra U,della Bella P,Elliott PM,Follath F,Gheorghiade M,Hasin Y,Hernborg A,Jaarsma T,Komajda M,Kornowski R,Piepoli M,Prendergast B,Tavazzi L,Vachiery JL,Verheugt FW,Zannad F.ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology.Developed in collaboration with the Heart Failure Association of the ESC(HFA)and endorsed by the European Society of Intensive Care Medicine(ESICM).Eur J Heart Fail.2008;10(10):933-989.
[3].Haffner SM,Lehto S,Ronnemaa T,Pyorala K,Laakso M.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.The New England journal of medicine.1998;339(4):229-234.
[4].Carrabba N,Valenti R,Parodi G,Santoro GM,Antoniucci D.Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation.2004;110(14):1974-1979.
[5].Norhammar A,Tenerz A,Nilsson G,Hamsten A,Efendic S,Ryden L,Malmberg K.Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus:a prospective study.Lancet.2002;359(9324):2140-2144.
[6].Greer JJ,Ware DP,Lefer DJ.Myocardial infarction and heart failure in the db/db diabetic mouse.Am J Physiol Heart Circ Physiol.2006;290(1):H146-153.
[7].Wencker D,Chandra M,Nguyen K,Miao W,Garantziotis S,Factor SM,Shirani J,Armstrong RC,Kitsis RN.A mechanistic role for cardiac myocyte apoptosis in heart failure.J Clin Invest.2003;111(10):1497-1504.
[8].Backlund T,Palojoki E,Saraste A,Eriksson A,Finckenberg P,Kyto V,Lakkisto P,Mervaala E,Voipio-Pulkki LM,Laine M,Tikkanen I.Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.Diabetologia.2004;47(2):325-330.
[9].Yoon YS,Uchida S,Masuo O,Cejna M,Park JS,Gwon HC,Kirchmair R,Bahlman F,Walter D,Curry C,Hanley A,Isner JM,Losordo DW.Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy:restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.Circulation.2005;111(16):2073-2085.
[10].Chandler MP,Morgan EE,McElfresh TA,KungTA,Rennison JH,Hoit BD,Young ME.Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats.Am J Physiol Heart Circ Physiol.2007;293(3):H 1609-1616.
[11].Popper SJ,Shimizu C,Shike H,Kanegaye JT,Newburger JW,Sundel RP,Brown PO,Burns JC,Relman DA.Gene-expression patterns reveal underlying biological processes in Kawasaki disease.Genome Biol.2007;8(12):R261.
[12].Flamez D,Berger V,Kruhoffer M,Orntoft T,Pipeleers D,Schuit FC.Critical role for cataplerosis via citrate in glucose-regulated insulin release.Diabetes.2002;51(7):2018-2024.
[13].Warnat P,Oberthuer A,Fischer M,Westermann F,Eils R,Brors B.Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes.BMC Cancer.2007;7:89.
[14].Feuvray D,Idell-Wenger JA,Neely JR.Effects of ischemia on rat myocardial function and metabolism in diabetes.Circulation research.1979;44(3):322-329.
[15].Lopaschuk GD,Spafford M.Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats.Circulation research.1989;65(2):378-387.
[16].Tani M,Neely JR.Hearts from diabetic rats are more resistant to in vitro ischemia:possible role of altered Ca2+ metabolism.Circulation research.1988;62(5):931-940.
[17].Khandoudi N,Bernard M,Cozzone P,Feuvray D.Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts.Cardiovascular research.1990;24(11):873-878.
[18].Khandoudi N,Bernard M,Cozzone P,Feuvray D.Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts.Diabetes.1995;44(2):196-202.
[19].Paulson DJ,Kopp SJ,Peace DG,Tow JP.Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats.J Appl Physiol.1988;65(1):187-193.
[20].Paulson DJ,Shug AL,Zhao J.Protection of the ischemic diabetic heart by L-propionylcarnitine therapy.Mol Cell Biochem.1992;116(1-2):131-137.
[21].Hsueh W,Abel ED,Breslow JL,Maeda N,Davis RC,Fisher EA,Dansky H,McClain DA,Mclndoe R,Wassef MK,Rabadan-Diehl C,Goldberg IJ.Recipes for creating animal models of diabetic cardiovascular disease.Circulation research. 2007;100(10):1415-1427.
[22].Pfeffer JM,Pfeffer MA,Braunwald E.Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure.Circulation.1987;75(1 Pt 2):I149-155.
[23].Litwin SE,Katz SE,Morgan JP,Douglas PS.Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat.Circulation.1994;89(1):345-354.
[24].Semeniuk LM,Kryski AJ,Severson DL Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.Am J Physiol Heart Circ Physiol.2002;283(3):H976-982.
[25].Paulson DJ.The diabetic heart is more sensitive to ischemic injury.Cardiovascular research.1997;34(1):104-112.
[26].Wohaieb SA,Godin DV.Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat.Effects of insulin treatment.Diabetes.1987;36(9):1014-1018.
[27].Tosaki A,Engelman DT,Engelman RM,Das DK.The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research.1996;31(4):526-536.
[28].Paulson DJ,Schmidt MJ,Romens J,Shug AL Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia:effects of L-acetylcarnitine.Basic Res Cardiol.1984;79(5):551-561.
[29].Higuchi M,Ikema S,Matsuzaki T,Hirayama K,Sakanashi M.Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts(?)solated from normal and diabetic rats.Journal of molecular ana(?)cellular cardiology.1991;23(2)(?)137-148.
[30].De Groote P,Lam(?)llin N,Mouquet F,Plichon D,Mc(?)adden E,Van Belle E,Bauters C.Impact of diabetes mellitus on long-term survival in patients with congestive heart failure.European heart journal.2004;25(8):656-662.
[31].McGuire DK,Newby LK,Bhapkar MV,Moliterno DJ,Hochman JS,Klein WW,Weaver WD,Pfisterer M,Corbalan R,Dellborg M,Granger CB,Van De Werf F,Topol EJ,Califf RM.Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.Am Heart J.2004;147(2):246-252.
[32].Jagasia D,McNulty PH.Diabetes mellitus and heart failure.Congest Heart Fail.2003;9(3):133-139;quiz 140-131.
[33].Raev DC.Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy?An echocardiographic study of young type I diabetic patients.Diabetes care.1994;17(7):633-639.
[34].Borges GR,de Oliveira M,Salgado HC,Fazan R,Jr.Myocardial performance in conscious streptozotocin diabetic rats.Cardiovascular diabetology.2006;5:26.
[35].Solomon SD,St John Sutton M,Lamas GA,Plappert T,Rouleau JL,Skali H,Moye L,Braunwald E,Pfeffer MA.Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.Circulation.2002;106(10):1251-1255.
[36].Yue P,Long CS,Austin R,Chang KC,Simpson PC,Massie BM.Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype.Journal of molecular and cellular cardiology.1998;30(8):1615-1630.
[37].Ono K,Matsumori A,Shioi T,Furukawa Y,Sasayama S.Cytokine gene expression after myocardial infarction in rat hearts:possible implication in left ventricular remodeling.Circulation.1998;98(2):149-156.
[38].Stanton LW,Garrard U,Damm D,Garrick BL,Lam A,Kapoun AM,Zheng Q,Protter AA,Schreiner GF,White RT.Altered patterns of gene expression in response to myocardial infarction.Circulation research.2000;86(9):939-945.
[39].Panes J,Kurose I,Rodriguez-Vaca D,Anderson DC,Miyasaka M,Tso P,Granger DN.Diabetes exacerbates inflammatory responses to ischemia-reperfusion.Circulation.1996;93(1):161-167.
[40].Xiao XH,Allen DG.Role of Na(+)/H(+)exchanger during ischemia and preconditioning in the isolated rat heart.Circulation research.1999;85(8):723-730.
[41].Ramasamy R,Schaefer S.Inhibition of Na+-H+ exchanger protects diabetic and non-diabetic hearts from ischemic injury:insight into altered susceptibility of diabetic hearts to ischemic injury.Journal of molecular and cellular cardiology.1999;31(4):785-797.
[42].Lagadic-Gossmann D,Buckler KJ,Le Prigent K,Feuvray D.Altered Ca2+handling in ventricular myocytes isolated from diabetic rats.The American journal of physiology.1996;270(5 Pt 2):H 1529-1537.
[43],Forrat R,Sebbag L,Wiernsperger N,Guidollet J,Renaud S,de Lorgeril M.Acute myocardial infarction in dogs with experimental diabetes.Cardiovascular research.1993;27(11):1908-1912.
[44].Ravingerova T,Neckar J,Kolar F.Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes.Molecular and cellular biochemistry.2003;249(1-2):167-174.
[45].Macgregor S,Zhao ZZ,Henders A,Nicholas MG,Montgomery GW,Visscher PM.Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays.Nucleic Acids Res.2008;36(6):e35.
[46].Bar-Joseph Z,Gifford DK,Jaakkola TS.Fast optimal leaf ordering for hierarchical clustering.Bioinformatics.2001;17 Suppl 1:S22-29.
[47].Liu H,Tarima S,Borders AS,Getchell TV,Getchell ML,Stromberg AJ.Quadratic regression analysis for gene discovery and pattern recognition for non-cyclic short time-course microarray experiments.BMC Bioinformatics.2005;6:106.
[48].Hosack DA,Dennis G,Jr.,Sherman BT,Lane HC,Lempicki RA.Identifying biological themes within lists of genes with EASE.Genome Biol.2003;4(10):R70.
[49].Tyagi SC,Rodriguez W,Patel AM,Roberts AM,Falcone JC,Passmore JC,Fleming JT,Joshua IG.Hyperhomocysteinemic diabetic cardiomyopathy:oxidative stress,remodeling,and endothelial-myocyte uncoupling.Journal of cardiovascular pharmacology and therapeutics.2005;10(1):1-10.
[50].Suleiman M,Aronson D,Asleh R,Kapeliovich MR,Roguin A,Meisel SR,Shochat M,Sulieman A,Reisner SA,Markiewicz W,Hammerman H,Lotan R,Levy NS,Levy AP.Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction.Diabetes.2005;54(9):2802-2806.
[51].Belke DD,Larsen TS,Gibbs EM,Severson DL.Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic(db/db)mice.Am J Physiol Endocrinol Metab.2000;279(5):E1104-1113.
[52].Chatham JC,Seymour AM.Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.Cardiovascular research.2002;55(1):104-112.
[53].An D,Rodrigues B.Role of changes in cardiac metabolism in development of diabetic cardiomyopathy.Am J Physiol Heart Circ Physiol.2006;291(4):H1489-1506.
[54].Smith HM,Hamblin M,Hill MF.Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure.Journal of molecular and cellular cardiology.2005;39(4):657-665.
[55].Cai L,Wang J,Li Y,Sun X,Wang L,Zhou Z,Kang YJ.Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy.Diabetes.2005;54(6):1829-1837.
[56].Nystrom T,Nygren A,Sjoholm A.Increased levels of tumour necrosis factor-alpha(TNF-alpha)in patients with Type Ⅱ diabetes mellitus after myocardial infarction are related to endothelial dysfunction.Clin Sci(Lond).2006;110(6):673-681.
[57].Giacchetti G,Sechi LA,Rilli S,Carey RM.The renin-angiotensin-aldosterone system,glucose metabolism and diabetes.Trends Endocrinol Metab.2005;16(3):120-126.
[58].Di Filippo C,Marfella R,Cuzzocrea S,Piegari E,Petronella P,Giugliano D,Rossi F,D'Amico M.Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.Diabetes.2005;54(3):803-810.
[59].Xu YJ,Chapman D,Dixon IM,Sethi R,Guo X,Dhalla NS.Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation.Journal of cellular and molecular medicine.2004;8(1):85-92.
[60].Pfeffer JM,Pfeffer MA,Fletcher PJ,Braunwald E.Progressive ventricular remodeling in rat with myocardial infarction.The American journal of physiology.1991;260(5 Pt 2):H1406-1414.
[61].Maisch B.Ventricular remodeling.Cardiology.1996;87 Suppl 1:2-10.
[62].Howard BV,Wylie-Rosett J.Sugar and cardiovascular disease:A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition,Physical Activity,and Metabolism of the American Heart Association.Circulation.2002;106(4):523-527.
[63].Cai L,Li W,Wang G,Guo L,Jiang Y,Kang YJ.Hyperglycemia-induced apoptosis in mouse myocardium:mitochondrial cytochrome C-mediated caspase-3 activation pathway.Diabetes.2002;51(6):1938-1948.
[64].Spierings D,McStay G,Saleh M,Bender C,Chipuk J,Maurer U,Green DR.Connected to death:the(unexpurgated)mitochondrial pathway of apoptosis.Science.2005;310(5745):66-67.
[65].Shiomi T,Tsutsui H,Ikeuchi M,Matsusaka H,Hayashidani S,Suematsu N,Wen J,Kubota T,Takeshita A.Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction.Journal of the American College of Cardiology.2003;42(1):165-172.
[66].Abbate A,Biondi-Zoccai GG,Baldi A.Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodeling.J Cell Physiol.2002;193(2):145-153.
[67].Zhang H,Li Q,Li Z,Mei Y,Guo Y.The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by analogous ischemia/reperfusion in vitro.Neurosci Res.2008;62(2):140-146.
[68].Chen N,Deng T,Chen P,Li L.[The regulation of apoptosis by Bcl-2,bcl-X(L),Bcl-2alpha and Bax in chronic liver disease].Zhonghua Nei Ke Za Zhi. 2000;39(12):808-810.
[69].Wong WW,Puthalakath H.Bcl-2 family proteins:the sentinels of the mitochondrial apoptosis pathway.IUBMB life.2008;60(6):390-397.
[70].Hishikawa K,Oemar BS,Nakaki T.Static pressure regulates connective tissue growth factor expression in human mesangial cells.J Biol Chem.2001;276(20):16797-16803.
[71].Way KJ,Isshiki K,Suzuma K,Yokota T,Zvagelsky D,Schoen FJ,Sandusky GE,Pechous PA,Vlahos CJ,Wakasaki H,King GL.Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2activation and diabetes.Diatbetes.2002;51(9):2709-2718.
[1]Diamant M,Lamb HJ,Groeneveld Y,et al.Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus.Journal of the American College of Cardiology 2003;42:328-35.
[2]Taegtmeyer H,McNulty P,Young ME.Adaptation and mahdaptation of the heart in diabetes:Part Ⅰ:general concepts.Circulation 2002;105:1727-33.
[3]Hayat SA,Patel B,Khattar RS,et at Diabetic cardiomyopathy:mechanisms,diagnosis and treatmnent.Clin Sci(Lond) 2004;107:539-57.
[4]Jagasia D,McNulty PH.Diabetes mellitus and heart failure.Congest Heart Fail 2003;9:133-9;quiz 40-1.
[5]Carrabba N,Valenti R,Parodi G,et at Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation 2004;110:1974-9.
[6]Haffner SM,Lehto S,Ronnemaa T,et al.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.The New England journal of medicine 1998;339:229-34.
[7]Janghorbani M,Hu FB,Willett WC,et al.Prospective study of type 1 and type 2diabetes and risk of stroke subtypes:the Nurses' Health Study.Diabetes care 2007;30:1730-5.
[8]Grundy SM,Cleeman JI,Merz CN,et al.Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel Ⅲ guidelines.Circulation 2004;110:227-39.
[9]Norhammar A,Tenerz A,Nilsson G,et al.Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus:a prospective study.Lancet 2002;:359:2140-4.
[10]Miettinen H,Lehto S,Salomaa V,et at Impact of diabetes on mortality after the first myocardial infarction.The FINMONICA Myocardial Infarction Register Study Group.Diabetes care 1998;21:69-75.
[11]McGuire DK,Newby LK,Bhapkar MV,et at Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.American heart journal 2004;147:246-52.
[12]Wagner AM,Martijnez-Rubio A,Ordonez-Llanos J,et al.Diabetes mellitus and cardiovascular disease.Eur J Intern Med 2002;13:15-30.
[13]Paulson DJ.The diabetic heart is more sensitive to ischemic injury.Cardiovascular research 1997;34:104-12.
[14]Feuvray D,Lopaschuk GD.Controversies on the sensitivity of the diabetic heart to ischemic injury:the sensitivity of the diabetic heart to ischemic injury is decreased.Cardiovascular research 1997;34:113-20.
[15]Lopaschuk GD,Spafford M.Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats.Circulation research 1989;65:378-87.
[16]Paulson DJ,Kopp SJ,Peace DG,et aL Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats.J Appl Physiol 1988;65:187-93.
[17]Paulson DJ,Shug AL,Zhao J.Protection of the ischemic diabetic heart by L-propionylcarnitine therapy.Mol Cell Biochem 1992;116:131-7.
[18]Khandoudi N,Bernard M,Cozzone P,et aL Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts.Cardiovascular research 1990;24:873-8.
[19]Wohaieb SA,Godin DV.Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat.Effects of insulin treatment.Diabetes 1987;36:1014-8.
[20]Tosaki A,Engelman DT,Engelman RM,et aL The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research 1996;31:526-36.
[21]Paulson DJ,Schmidt MJ,Romens J,et aL Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia:effects of L-acetylcarnitine.Basic Res Cardiol 1984;79:551-61.
[22]Higuchi M,Ikema S,Matsuzaki T,et aL Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts isolated from normal and diabetic rats.Journal of molecular and cellular cardiology 1991;23:137-48.
[23]Capes SE,Hunt D,Malmberg K,et aL Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes:a systematic overview.Lancet 2000;355:773-8.
[24]Oswald GA,Corcoran S,Yudkin JS.Prevalence and risks of hyperglycaemia and undiagnosed diabetes in patients with acute myocardial infarction.Lancet 1984;1:1264-7.
[25]Kosiborod M,Rathore SS,Inzucchi SE,et al.Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction:implications for patients with and without recognized diabetes.Circulation 2005;111:3078-86.
[26]Meier JJ,Deifuss S,Khmann A,et al.Phsma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes:the Langendreer Myocardial Infarction and Blood Glucose in Diabetic Patients Assessment(LAMBDA).Diabetes care 2005;28:25.51-3.
[27]L L,Van den Berghe G.Glucose metabolism and insulin therapy.Crit Care Clin 2006;22:119-29,ⅶ.
[28]Malmberg K.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus.DIGAMI(Diabetes Mellitus,Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.BMJ 1997;314:1512-5.
[29]Deedwania P,Kosiborod M,Barrett E,et al.Hyperglycemia and acute coronary syndrome:a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition,Physical Activity,and Metabolism.Anesthesiology 2008;109:14-24.
[30]Esposito K,Nappo F,Marfella R,et al.Inflammatory.cytokine concentrations are acutely increased by hyperglycemia in humans:role of oxidative stress.Circulation 2002;106:2067-72.
[31]Haber CA,Lam TK,Yu Z,et al.N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo:possible role of oxidative stress.Am J Physiol Endocrinol Metab 2003;285:E744-53.
[32]Suleiman M,Hammerman H,Boulos M,et al.Fasting glucose is an important independent risk factor for 30-day mortality in patients with acute myocardial infarction:a prospective study.Circulation.2005;111:754-60.
[33]中国心脏调查组.中国住院冠心病患者糖代谢异常研究-中国心脏调查.中华内分泌杂志 2006;22:7-10.
[34]Hadjadj S,Coisne D,Mauco G,et al.Prognostic value of admission plasma glucose and HbA in acute myocardial infarction.Diabet Med 2004;21:305-10.
[35]Ryden L,Standl E,Bartnik M,et al.Guidelines on diabetes,pre-diabetes,and cardiovascular diseases:executive summary.The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology(ESC) and of the European Association for the Study of Diabetes(EASD).European heart journal 2007;28:88-136.
[36]van den Berghe G,Wouters P,Weekers F,et al.Intensive insulin therapy in the critically ill patients.The New England journal of medicine 2001;345:1359-67.
[37]Malmberg K,Ryden L,Wedel H,et al.Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction(DIGAMI 2):effects on mortality and morbidity.European heart journal 2005;26:650-61.
[1]Song GY,Wu YJ,Yang YJ,et al.Diabetes mellitus can accerate the progression of post-infarction genetic regulatory expression in untreated Streptozotocin-induced Diabetic Rat Model.ESC Acute Cardiac Care Abstract 2008.
[2]Tosaki A,Engelman DT,Engelman RM,et al.The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts.Cardiovascular research 1996;31:526-36.
[3]Semeniuk LM,Kryski AJ,Severson DL.Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.Am J Physiol Heart Circ Physiol 2002;283:H976-82.
[4]Rajan SK,Gokhale SM.Cardiovascular function in patients with insulin-dependent diabetes mellitus:a study using noninvasive methods.Ann N Y Acad Sci 2002;958:425-30.
[5]Joffe,Ⅱ,Travers KE,Perreault-Micale CL,et al Abnormal cardiac function in the streptozotocin-induced non-insulin-dependent diabetic rat:noninvasive assessment with doppler echocardiography and contribution of the nitric oxide pathway.Journal of the American College of Cardiology 1999;34:2111-9.
[6]Trost SU,Belke DD,Bluhm WF,et al.Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in diabetic cardiomyopathy.Diabetes 2002;51:1166-71.
[7]Poirier P,Bogaty P,Garneau C,et al.Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes:importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy.Diabetes care 2001;24:5-10.
[8]Schannwell CM,Schneppenheim M,Perings S,et al.Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy.Cardiology 2002;98:33-9.
[9]Friedman NE,Levitsky LL,Edidin DV,et aL Echocardiographic evidence for impaired myocardial performance in children with type I diabetes mellitus.Am J Med 1982;73:846-50.
[10]Mizushige K,Yao L,Noma T,et al.Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type Ⅱ diabetic rat model.Circulation 2000;101:899-907.
[11]Cai L,Wang J,Li Y,et aL Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy.Diabetes 2005;54:1829-37.
[12]Regan TJ,Lyons MM,Ahmed SS,et aL Evidence for cardiomyopathy in familial diabetes mellitus.J Clin Invest 1977;60:884-99.
[13]Nunoda S,Genda A,Sugihara N,et al.Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus.Heart Vessels 1985;1:43-7.
[14]Vitolo E,Madoi S,Sponzilli C,et al.Vectorcardiographic evaluation of diabetic cardiomyopathy and of its contributing factors.Acta Diabetol hat 1988;25:227-34.
[15]Fang ZY,Yuda S,Anderson V,et al.Echocardiographic detection of early diabetic myocardial disease.Journal of the American College of Cardiology 2003;41:611-7.
[16]Chatham JC,Seymour AM.Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.Cardiovascular research 2002;55:104-12.
[17]Garvey WT,Hardin D,Juhaszova M,et aL Effects of diabetes on myocardial glucose transport system in rats:implications for diabetic cardiomyopathy.The American journal of physiology 1993;264:H837-44.
[18]Nakayama H,Morozumi X Nanto S,et aL Abnormal myocardial free fatty acid utilization deteriorates with morphological changes in the hypertensive heart.Jpn CircJ 2001;65:783-7.
[19]Malhotra A,Sanghi V.Regulation of contractile proteins in diabetic heart.Cardiovascular research 1997;34:34-40.
[20]Dhalla NS,Liu X,Panagia V,et aL Subcellular remodeling and heart dysfunction in chronic diabetes.Cardiovascular research 1998;40:239-47.
[21]Abe X Ohga Y,Tabayashi N,et al.Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats.Am J Physiol Heart Circ Physiol 2002;282:H138-48.
[22]Yoon YS,Uchida S,Masuo O,et aL Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy:restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.Circulation 2005;111:2073-85.
[23]Haunstetter A,Izumo S.Apoptosis:basic mechanisms and implications for cardiovascular disease.Circulation research 1998;82:1111-29.
[24]Li B,Setoguchi M,Wang X,et aL Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart.Circulation research 1999;84:1007-19.
[25]Fiordaliso F,Leri A,Cesselli D,et aL Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death.Diabetes 2001;50:2363-75.
[26]Chen S,Evans T,Mukherjee K,et aL Diabetes-induced myocardial structural changes:role of endothelin-1 and its receptors.Journal of molecuhr and cellular cardiology 2000;32:1621-9.
[27]Cai L,Li W,Wang G,et aL Hyperglycemia-induced apoptosis in mouse myocardium:mitochondrial cytochrome C-mediated caspase-3 activation pathway.Diabetes 2002;51:1938-48.
[28]Kajstura J,Fiordaliso F,Andreoli AM,et aL IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin Ⅱ-mediated oxidative stress.Diabetes 2001;50:1414-24.
[29]Hayat SA,Patel B,Khattar RS,et aL Diabetic cardiomyopathy:mechanisms,diagnosis and treatment.Clin Sci(Lond)2004;107:539-57.
[30]Nitenberg A,Valensi P,Sachs R,et al.Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.Diabetes 1993;42:1017-25.
[31]Meyer C,Schwaiger M.Myocardial blood flow and glucose metabolism in diabetes mellitus.The American journal of cardiology 1997;80:94A-101A.
[32]Johnstone MT,Creager SJ,Scales KM,et aL Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.Circulation 1993;88:2510-6.
[33]Taylor PD,Graves JE,Poston L.Selective impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated resistance arteries of the streptozotocin-induced diabetic rat.Clin Sci(Lond)1995;88:519-24.
[34]Bucala R,Tracey KJ,Cerami A.Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.J Clin Invest 1991;87:432-8.
[35]Rosen P,Ballhausen T,Bloch W,et aL Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart influence of tocopherol as antioxidant.Diabetologia 1995;38:1157-68.
[36]Tesfamariam B,Jakubowski JA,Cohen RA.Contraction of diabetic rabbit aorta caused by endothelium-derived PGH2-TxA2.The American journal of physiology 1989;257:H1327-33.
[37]Koya D,King GL.Protein kinase C activation and the development of diabetic complications.Diabetes 1998;47:859-66.
[38]Fernandez-Real JM,Lainez B,Vendrell J,et aL Shedding of TNF-alpha receptors,btood pressure,and insulin sensitivity in type 2 diabetes mellitus.Am J Physiol Endocrinol Metab 2002;282:E952-9.
[39]Quilliot D,Fluckiger L,Zannad F,et aL Impaired autonomic control of heart rate and blood pressure in obesity:role of age and of insulin-resistance.Clin Auton Res 2001;11:79-86.
[40]de Kreutzenberg SV,Avogaro A,Tiengo A,et aL Left ventricular mass in type 2 diabetes mellitus.A study employing a simple ECG index:the Cornell voltage.J Endocrinol Invest 2000;23:139-44.
[41]Hirayama H,Sugano M,Abe N,et aL Troglitazone,an antidiabetic drug,improves left ventricular mass and diastolic function in normotensive diabetic patients.Int J Cardiol 2001;77:75-9.
[42]Hintz KK,Ren J.Prediabetic insulin resistance is not permissive to the development of cardiac resistance to insulin-like growth factor I in ventricular myocytes.Diabetes Res Clin Pract 2002;55:89-98.
[43]Rutter MK,Parise H,Benjamin EJ,et aL Impact of glucose intolerance and insulin resistance on cardiac structure and function:sex-related differences in the Framingham Heart Study.Circulation 2003;107:448-54.
[44]Estep JD,Aguilar D.Diabetes and heart failure in the post-myocardial infarction patient.Curr Heart Fail Rep 2006;3:164-9.
[45]Aguilar D,Solomon SD,Kober L,et aL Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction:the VALsartan In Acute myocardial iNfarcTion(VALIANT)triaL Circulation 2004;110:1572-8.
[46]Murcia AM,Hennekens CH,Lamas GA,et aL Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction.Arch Intern Med 2004;164:2273-9.
[47]Mak KH,Moliterno DJ,Granger CB,et al.Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction.GUSTO-I Investigators.Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.Journal of the American College of Cardiology 1997;30:171-9.
[48]Woodfield SL,Lundergan CF,Reiner JS,et al.Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction:the GUSTO-I experience.Journal of the American College of Cardiology 1996;28:1661-9.
[49]Prasad A,Stone GW,Stuckey TD,et al.Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction.Journal of the American College of Cardiology 2005;45:508-14.
[50]Solomon SD,St John Sutton M,Lamas GA,et al.Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.Circulation 2002;106:1251-5.
[51]Carrabba N,Valenti R,Parodi G,et al.Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction.Circulation 2004;110:1974-9.
[52]Chandler MP,Morgan EE,McElfresh TA,et al.Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats.Am J Physiol Heart Circ Physiol 2007;293:H1609-16.
[53]Suleiman M,Aronson D,Asleh R,et al.Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction.Diabetes 2005;54:2802-6.
[54]An D,Rodrigues B.Role of changes in cardiac metabolism in devetopment of diabetic cardiomyopathy.Am J Physiol Heart Circ Physiol 2006;291:H1489-506.
[55]Nystrom T,Nygren A,Sjoholm A.Increased levels of tumour necrosis factor-alpha(TNF-alpha)in patients with Type Ⅱ diabetes mellitus after myocardial infarction are related to endothelial dysfunction.Clin Sci(Lond)2006;110:673-81.
[56]Giacchetti G,Sechi LA,Rilli S,et al.The renin-angiotensin-aldosterone system,glucose metabolism and diabetes.Trends Endocrinol Metab 2005;16:120-6.
[57]Backlund T,Palojoki E,Saraste A,et al.Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.Diabetologia 2004;47:325-30.
[58]Tyagi SC,Rodriguez W,Patel AM,et al.Hyperhomocysteinemic diabetic cardiomyopathy:oxidative stress,remodeling,and endothelial-myocyte uncoupling.Journal of cardiovascular pharmacology and therapeutics 2005;10:1-10.
[59]Smith HM,Hamblin M,Hill MF.Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure.Journal of molecular and cellular cardiology 2005;39:657-65.
[60]Di Filippo C,Marfella R,Cuzzocrea S,et al.Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.Diabetes 2005;54:803-10.