分泌型磷脂酶A2、高敏C反应蛋白与冠状动脉病变相关性研究及其临床意义
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摘要
研究背景
冠心病是威胁人类健康的主要疾病之一,在有些国家,由冠状动脉粥样硬化引起的心脏病(冠心病)已成为人群中首位的死亡原因。目前冠心病的发病机制尚未完全阐明,近年的研究表明,炎症是冠心病发生发展过程中的核心因素。通过检测血清中炎性因子的水平,能够间接反映冠心病的病变程度以及斑块的易损性。
作为炎症因子之一,分泌型磷脂酶A2(sPLA2)为脂蛋白相关性磷脂酶A2的亚型之一,主要由血管壁平滑肌细胞与巨噬细胞等产生,属于钙依赖的磷脂酶家族,主要位于巨噬细胞集聚区、脂质核心区以及病变内膜的细胞外基质内。目前认为,sPLA2与动脉粥样硬化的发生发展相关,可能机制是水解细胞膜及脂蛋白的磷脂酰胆碱,并产生致炎症反应及动脉粥样硬化的溶血磷脂胆碱(LysoPC)和氧化脂肪酸(OxFA)[1]。Hs-CRP在冠心病发病中的作用已日益受到重视,其价值明显高于传统的冠心病危险因素生化指标,其血清水平同临床心血管病有浓度依赖关系,可以作为预测冠心病事件的独立因子[2、3]。
目的
本研究以冠脉造影正常者为对照组,研究各组冠心病患者血清中sPLA2、hs-CRP水平的变化特点,冠状动脉粥样硬化斑块性质与血清中sPLA2、hs-CRP水平的相关性以及介入治疗对血清中sPLA2、hs-CRP水平的影响,探讨sPLA2、hs-CRP在冠心病发病机制中的作用,以及检测血清中sPLA2、hs-CRP水平在冠心病诊疗中的价值。
方法
冠心病患者104例,男66例,女38例,其中稳定型心绞痛(SA)28例、不稳定型心绞痛(UA)54例、急性心肌梗塞(AMI)22例。所有患者均行冠状动脉造影术。冠状动脉造影显示至少一支主要冠状动脉存在病变,部分单支病变患者在行经皮冠脉介入治疗(PCI)前进行IVUS检查。另外选择冠状动脉造影正常者20例为对照组。
所有患者均在采血前禁食10小时以上,并于次日清晨空腹采血5ml;所有患者均分别于术前即刻、术后即刻、术后6小时、术后24小时采血5ml,采用双抗体夹心酶联免疫吸附法(ELISA)测定血清中sPLA2的浓度,并采用乳胶增强免疫比浊法测定血清中hs-CRP的浓度。所有数据资料用SPSS11.5软件包行统计学处理。P<0.05为差异有统计学意义,P<0.01为差异有显著统计学意义。
结果
1. AMI组、UA组、SA组和NS组血清sPLA2、hs-CRP水平两两比较,差异均有显著统计学意义(P﹤0.01)。设定以sPLA2大于50.00pg/ml为阳性判断标准,各组阳性率分别为100%、90%、55%和5%。
2.冠脉造影正常对照组术前术后血清sPLA2、hs-CRP水平无明显变化(P﹥0.05)。PCI患者,术后血清sPLA2、hs-CRP水平较术前明显升高,差异有统计学意义(P﹤0.01)(AMI组术后即刻血清hs-CRP水平较术前即刻比较,P﹤0.05)。
3.软斑块组血清sPLA2、hs-CRP水平与纤维斑块组、钙化斑块组比较,差异有显著统计学意义(P﹤0.01);纤维斑块血清sPLA2水平与钙化斑块组比较,差异有显著统计学意义(P﹤0.01),血清hs-CRP水平与钙化斑块组比较,差异有统计学意义(P﹤0.05)。向心性斑块组血清sPLA2水平与偏心性斑块组比较,差异有显著统计学意义(P﹤0.01);hs-CRP水平与偏心性斑块组比较,差别有统计学意义(P﹤0.05)。
结论
1. sPLA2、hs-CRP参与了冠心病的发生发展,可作为冠脉病变程度及病情变化的预测因子,辅助冠心病的诊疗。
2.PCI造成冠状动脉内膜损伤或斑块破裂,短期内触发或加重了冠状动脉局部炎症反应。sPLA2、hs-CRP参与了冠状动脉局部炎症。血清sPLA2、hs-CRP水平可能间接反映冠状动脉局部炎症程度。
3.血清sPLA2、hs-CRP水平有可能间接反应斑块的性质及其偏心程度,判断斑块的易损性。
Background:
Coronary artery disease (CAD) is one of the principal diseases that threaten human health so much that it’s the primar cause of death in some countries. At present, the pathogenesy of CAD is not fully studied. Current studies have shown that inflammation plays an essential role in the development and procedure of CAD. The extent of pathological changes and vulnerability of plaque can be determined indirectly by serum inflammatory factor level.
As one of the inflammation factors,secretory type II phosphatidolipase A2, a subtype of lipoprotein-related phosphatidolipase A2, is mainly produced by smooth muscle cells and macrophages and belongs to calcium-depended phosphatidolipase family, which locates mainly in macrophages gathering place, lipid core area and extracellular matrix of pathological intima. Currently, it’s thought to be related with the development of atherosclerosis by possibly hydrolyzing cellular membrane and phosphatidylcholine in lipoprotein to produce proinflammatory reaction and atherosclerotic lysophosphatidylcholine (LysoPC) and oxidized fatty acid (OxFA) [1]. Increasing evidence has shown that hs-CRP plays an important role in the development of CAD which is considered as An independent prediction factor because its serum concentrated-depende- nt relationship with cardiovascular events[2,3].
Objective:
This study aimed to study the character of serum level changes of sPLA2 and hs-CRP in every group patients with CAD, the dependability between atherosclerotic plaque features and serum levels of sPLA2 and hs-CRP, and the influence of intervention therapy on serum levels of sPLA2 and hs-CRP. To explore the role of sPLA2 and hs-CRP in CAD pathogenesy and the value of serum level of sPLA2 and hs-CRP in CAD diagnosis and theropy.
Methods:
One hundred and four patients (male 66, female 38) with CAD were enrolled in this study including stable angina (SA) 28, unstable angina (UA) 54 and acute myocardium infarction (22). All patients underwent coronary angiography with pathological changes in at least one coronary artery. Intravascular ultrasound (IVUS) was performed before percutaneous coronary intervention (PCI) in partly patients. In addition, 20 patients with normal CAG served as control.
5 ml of blood was taken from all patients without food over 10 h before blood taken. Blood was taken before and 0, 6, 24h after intervention, respectively. Serum sPLA2 level was measured by double antibody enzyme linked immunoysorbent assay (ELISA) and hs-CRP by emulsion reinforced immunoturbidimetry (ITM). All results were statistically analyzed with SPSS 11.5. P<0.05 was considered statistic difference , P<0.01 was considered significantly statistic difference.
Results:
1. Compared with each other, serum levels of sPLA2 and hs-CRP are statistically different in AMI, UA, SA and NS groups (p<0.01).The positive standard of sPLA2 is considered as 50pg/ml, positive ratio is 100%, 90%, 55% and 5% in AMI, UA , SA and NS group.
2. Serum levels of sPLA2 and hs-CRP didn’t change much before and after intervention in NS group while in the patients with PCI the serum levels of sPLA2 and hs-CRP increased significantly after intervention (p<0.01) (in AMI group, p<0.05 compared with those before imtervention).
3. Serum levels of sPLA2 and hs-CRP were statistically higher in soft plaque group compared with fibrous plaque group and calcified plaque group (p<0.01). In fibrous plaque group, serum levels of sPLA2 and hs-CRP were significantly higher than those in calcified plaque group, p<0.01 and p<0.05, respectively. The same as that, in afferens plaque group and eccentricity plaque group.
Conclusions:
1. sPLA2 and hs-CRP play important roles in the development of CAD and can be considered as a predict factor in the diagnosis of CAD.
2. PCI results in intima damage in coronary artery and plaque rupture and triggers or aggravates local inflammation reaction. sPLA2 and hs-CRP took part in local inflammation in coronary artery .The serum level of sPLA2 and hs-CRP may indirectly reflect local inflammation in coronary artery.
3. Serum levels of sPLA2 and hs-CRP could reflect plaque characters such as eccentricity and vulnerability.
冠心病是威胁人类健康的主要疾病之一,在有些国家,由冠状动脉粥样硬化引起的心脏病(冠心病)已成为人群中首位的死亡原因。目前冠心病的发病机制尚未完全阐明,近年的研究表明,炎症是冠心病发生发展过程中的核心因素。通过检测血清中炎性因子的水平,能够间接反映冠心病的病变程度以及斑块的易损性。
作为炎症因子之一,分泌型磷脂酶A2(sPLA2)为脂蛋白相关性磷脂酶A2的亚型之一,主要由血管壁平滑肌细胞与巨噬细胞等产生,属于钙依赖的磷脂酶家族,主要位于巨噬细胞集聚区、脂质核心区以及病变内膜的细胞外基质内。目前认为,sPLA2与动脉粥样硬化的发生发展相关,可能机制是水解细胞膜及脂蛋白的磷脂酰胆碱,并产生致炎症反应及动脉粥样硬化的溶血磷脂胆碱(LysoPC)和氧化脂肪酸(OxFA)[1]。Hs-CRP在冠心病发病中的作用已日益受到重视,其价值明显高于传统的冠心病危险因素生化指标,其血清水平同临床心血管病有浓度依赖关系,可以作为预测冠心病事件的独立因子[2、3]。
目的
本研究以冠脉造影正常者为对照组,研究各组冠心病患者血清中sPLA2、hs-CRP水平的变化特点,冠状动脉粥样硬化斑块性质与血清中sPLA2、hs-CRP水平的相关性以及介入治疗对血清中sPLA2、hs-CRP水平的影响,探讨sPLA2、hs-CRP在冠心病发病机制中的作用,以及检测血清中sPLA2、hs-CRP水平在冠心病诊疗中的价值。
方法
冠心病患者104例,男66例,女38例,其中稳定型心绞痛(SA)28例、不稳定型心绞痛(UA)54例、急性心肌梗塞(AMI)22例。所有患者均行冠状动脉造影术。冠状动脉造影显示至少一支主要冠状动脉存在病变,部分单支病变患者在行经皮冠脉介入治疗(PCI)前进行IVUS检查。另外选择冠状动脉造影正常者20例为对照组。
所有患者均在采血前禁食10小时以上,并于次日清晨空腹采血5ml;所有患者均分别于术前即刻、术后即刻、术后6小时、术后24小时采血5ml,采用双抗体夹心酶联免疫吸附法(ELISA)测定血清中sPLA2的浓度,并采用乳胶增强免疫比浊法测定血清中hs-CRP的浓度。所有数据资料用SPSS11.5软件包行统计学处理。P<0.05为差异有统计学意义,P<0.01为差异有显著统计学意义。
结果
1. AMI组、UA组、SA组和NS组血清sPLA2、hs-CRP水平两两比较,差异均有显著统计学意义(P﹤0.01)。设定以sPLA2大于50.00pg/ml为阳性判断标准,各组阳性率分别为100%、90%、55%和5%。
2.冠脉造影正常对照组术前术后血清sPLA2、hs-CRP水平无明显变化(P﹥0.05)。PCI患者,术后血清sPLA2、hs-CRP水平较术前明显升高,差异有统计学意义(P﹤0.01)(AMI组术后即刻血清hs-CRP水平较术前即刻比较,P﹤0.05)。
3.软斑块组血清sPLA2、hs-CRP水平与纤维斑块组、钙化斑块组比较,差异有显著统计学意义(P﹤0.01);纤维斑块血清sPLA2水平与钙化斑块组比较,差异有显著统计学意义(P﹤0.01),血清hs-CRP水平与钙化斑块组比较,差异有统计学意义(P﹤0.05)。向心性斑块组血清sPLA2水平与偏心性斑块组比较,差异有显著统计学意义(P﹤0.01);hs-CRP水平与偏心性斑块组比较,差别有统计学意义(P﹤0.05)。
结论
1. sPLA2、hs-CRP参与了冠心病的发生发展,可作为冠脉病变程度及病情变化的预测因子,辅助冠心病的诊疗。
2.PCI造成冠状动脉内膜损伤或斑块破裂,短期内触发或加重了冠状动脉局部炎症反应。sPLA2、hs-CRP参与了冠状动脉局部炎症。血清sPLA2、hs-CRP水平可能间接反映冠状动脉局部炎症程度。
3.血清sPLA2、hs-CRP水平有可能间接反应斑块的性质及其偏心程度,判断斑块的易损性。
Background:
Coronary artery disease (CAD) is one of the principal diseases that threaten human health so much that it’s the primar cause of death in some countries. At present, the pathogenesy of CAD is not fully studied. Current studies have shown that inflammation plays an essential role in the development and procedure of CAD. The extent of pathological changes and vulnerability of plaque can be determined indirectly by serum inflammatory factor level.
As one of the inflammation factors,secretory type II phosphatidolipase A2, a subtype of lipoprotein-related phosphatidolipase A2, is mainly produced by smooth muscle cells and macrophages and belongs to calcium-depended phosphatidolipase family, which locates mainly in macrophages gathering place, lipid core area and extracellular matrix of pathological intima. Currently, it’s thought to be related with the development of atherosclerosis by possibly hydrolyzing cellular membrane and phosphatidylcholine in lipoprotein to produce proinflammatory reaction and atherosclerotic lysophosphatidylcholine (LysoPC) and oxidized fatty acid (OxFA) [1]. Increasing evidence has shown that hs-CRP plays an important role in the development of CAD which is considered as An independent prediction factor because its serum concentrated-depende- nt relationship with cardiovascular events[2,3].
Objective:
This study aimed to study the character of serum level changes of sPLA2 and hs-CRP in every group patients with CAD, the dependability between atherosclerotic plaque features and serum levels of sPLA2 and hs-CRP, and the influence of intervention therapy on serum levels of sPLA2 and hs-CRP. To explore the role of sPLA2 and hs-CRP in CAD pathogenesy and the value of serum level of sPLA2 and hs-CRP in CAD diagnosis and theropy.
Methods:
One hundred and four patients (male 66, female 38) with CAD were enrolled in this study including stable angina (SA) 28, unstable angina (UA) 54 and acute myocardium infarction (22). All patients underwent coronary angiography with pathological changes in at least one coronary artery. Intravascular ultrasound (IVUS) was performed before percutaneous coronary intervention (PCI) in partly patients. In addition, 20 patients with normal CAG served as control.
5 ml of blood was taken from all patients without food over 10 h before blood taken. Blood was taken before and 0, 6, 24h after intervention, respectively. Serum sPLA2 level was measured by double antibody enzyme linked immunoysorbent assay (ELISA) and hs-CRP by emulsion reinforced immunoturbidimetry (ITM). All results were statistically analyzed with SPSS 11.5. P<0.05 was considered statistic difference , P<0.01 was considered significantly statistic difference.
Results:
1. Compared with each other, serum levels of sPLA2 and hs-CRP are statistically different in AMI, UA, SA and NS groups (p<0.01).The positive standard of sPLA2 is considered as 50pg/ml, positive ratio is 100%, 90%, 55% and 5% in AMI, UA , SA and NS group.
2. Serum levels of sPLA2 and hs-CRP didn’t change much before and after intervention in NS group while in the patients with PCI the serum levels of sPLA2 and hs-CRP increased significantly after intervention (p<0.01) (in AMI group, p<0.05 compared with those before imtervention).
3. Serum levels of sPLA2 and hs-CRP were statistically higher in soft plaque group compared with fibrous plaque group and calcified plaque group (p<0.01). In fibrous plaque group, serum levels of sPLA2 and hs-CRP were significantly higher than those in calcified plaque group, p<0.01 and p<0.05, respectively. The same as that, in afferens plaque group and eccentricity plaque group.
Conclusions:
1. sPLA2 and hs-CRP play important roles in the development of CAD and can be considered as a predict factor in the diagnosis of CAD.
2. PCI results in intima damage in coronary artery and plaque rupture and triggers or aggravates local inflammation reaction. sPLA2 and hs-CRP took part in local inflammation in coronary artery .The serum level of sPLA2 and hs-CRP may indirectly reflect local inflammation in coronary artery.
3. Serum levels of sPLA2 and hs-CRP could reflect plaque characters such as eccentricity and vulnerability.
引文
[1] Carpenter KL,Dennis IF,Challis IR,et al.Inhibition of lipoprotein- associated phospholipase A2 diminishes the death- inducing effects of oxidised LDL on human monocytemacrophages[J].FEBS Lett,2001,505: 357–363.
[2] Danesh J,Wheeler JR,Hirschfield GM,et al.C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart diseasa[J].N Engl J Med.2004,350:1387-1397.
[3] Ridker PM,Hennekens CH,Buring JE,et al.C-reactive protein and other markers of inflammation in the cardiovascular disease in Women[J].N Engl J Med.2003,342:836-843.
[4] 陈国伟,郑宗锷,主编.现代心脏内科学.第二版.湖南长沙:湖南科学技术出版社,2002.1037-1038.
[5] YANG Ping,HANG Yonglun,WEN Xianyong,et al.Clinical Significance of Inflammatory Markers in Patients with Coronary Heart Disease[J].J Med Theor&Prac Vo1.20,No.1,Jan2007:9-10.
[6] Six DA,Dennis EA.The expanding superfamily of phospholipase A2 enzymes:classification and characterization[J].Biochim Biophys Acta ,2000,1488(1-2):1-19.
[7] Kolodgie FD,Burke AP,Taye A, et al.Lipoprotein- associated phospholipase A2 is highly expressed in macrophages of coronary lesions prone to rupture[J].Circulation,2004,110 (suppl III):246-247.
[8] Macphee CH .Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target[J].Curr Opin Pharmacol,2001, 1:121-125.
[9] 陈莉延.磷脂酶 A2 的研究进展[J].国外医学生理、病理科学与临床册,2000,20(6):473-476.
[10] 陆青,杨海敏.全身 CRP 测定仪及其试剂的评估[J].上海医学检验杂志,1999,14(5):268– 269.
[11]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.慢性稳定性心绞痛诊断与治疗指南[J].中华心血管病杂志,2007,35(3)3:195-206.
[12]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.不稳定型心绞痛诊断和治疗建议[J].中华心血管病杂志,2000,28(6):409-412.
[13]中华医学会心血管病学分会,中华心血管病杂志编辑委员会,中国循环杂志编辑委员会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,12(29)12:710-725.
[14] 葛均波.血管内超声波多普勒学.北京:人民卫生出版社,2000:114.
[15] Shah PK. Mechanisms of plaque vulnerability and rupture[J].J Am Coil Cardiol,2003,41(4 Suppl S):15S--22S.
[16] 杨立明,赵宝春.不同类型炎症C一反应蛋白水平的差异与冠心病的关系[J]. 中国煤炭工业医学杂志,2007,3(1O),3:275-276.
[17] Etri T,Kovan en,Markku O,et a1.Secretory Group11 PhospholipaseA2,A newly Recognized Acute — Phase Reactant With a Role in Atherogenesis Editoria1.Circulation Research,2O00,86:610.
[18] Kimura-Matsumoto M, Ishikawa Y, Komiyama K,et al. Expression of secretory phospholipase A2s in human atherosclerosis development. Atherosclerosis. 2007,Mar:10. [Epub ahead of print]
[19] Ghesquiere S,Gijbels M,Anthonsen M,van Gorp P,van der Made I, Johansen B,et al.Macrophage2specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition[J].J Lipid Res,2005,46(2):201-210.
[20] Hurt-Camejo E ,Camejo G,Sartipy P.Phospholipase A2 and small,dense low density lipoprotein[J].Curr Opin Lipidol,2000,11(5):465-471.
[21] 于路,傅国胜,姜文兵等.冠心病患者分泌型磷脂酶 A2 与冠状动脉病变积分及动脉硬化指数的相关性[J].中国介入心脏病学杂志,2007,2(15):31-33.
[22] Niessen H , Krijnen P , Visser C , Meijer C , Eric Hack C. Type II secretory phospholipase A2 in cardiovascular disease : a mediator in atherosclerosis and ischemic damage to cardiomyocytes[J]. Cardiovasc Res,2003,60(1):68-77.
[23] 于路,姜文兵,傅国胜等.冠心病患者分泌型磷脂酶 A2 的变化及其高敏 C反应蛋白的关系[J].中国动脉硬化杂志,2006,14(10):884-886.
[24] Ziad Mallat, Joelle Benessiano, Tabassome Simon,et al. Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women The EPIC-NORFOLK Study[J].Arterioscler Thromb Vasc Biol. 2007;27:1177 -1183.
[25] Messer J V.C-reactive protein and cardiovascular disease[J]. Circul ation,2006, 114:253-254.
[26] 马腾,吴继雄,孙昕. 血清 C-反应蛋白、可溶性 CD40 配体、基质金属蛋白酶-2 水平与冠心病的相关性[J]. 临床心血管病杂志.2007,3(23)3:170-173.)
[27] Zwaka TP,Hombach V,Torzewski J.C—reactive protein mediated low density lipoprotein uptake by macrophages : implications for atherosclerosis [J].Circulation;2001,103(6):1194—1197.
[28] Nakagomi A , Freedman SB , Geczy CL . Interferongamma and lipopolysaccharide potentiate monocyte tissue factor induction by C —reactive protein:relationship with age,sex,and hormone replacement treatment[J].Circulation,2000,101(10):1784—1791.
[29] Yasojima K,Schwab C,Mcgeer EG,et a1.Generation of C—reactive protein and complement components in atherosclerotic plaques[J].Am J Pathol,2001,158(7):1039—1049.)
[30] Person GR.Pettemson T.Ohlsson 0.Renvert S.High—sensitivity serun C- —reactive protein levels in subjects with or without myocardialinfarction or periodontitis,[J].J Clin Periodontol.20O5.32(3):219—224.
[31]Taniguchi H.Momiyama Y.Ohmofi R.Yonemura A.Yanmshita T.Tamai S.et a1.Associations of plasma C-reactive protein leveh with the presence and extent of coronary stenosis in patiens with stable coronary artery disease [J]. Atheroscerosis.2OO5.178(1):173-l77.)
[32]齐藤宪祜.超敏-CRP(hs-CRP)在临床的新应用[G].第五届中日临床技术研讨 会论文汇编,2002,10:30-31.
[33]郑刚,张承中.高敏 C 反应蛋白与急性冠状动脉综合症相关的临床证据[J].中国动脉硬化杂志,2003,11(7):691-694.
[34]Ahmed JM,Mintz GS,Weissman NJ,et a1.Mechanism of lumen enlargement during intracoronary stent implantation:an intravascular ultrasound study[J].Circulation,2000,102(1):7210
[35]Ping-YenLiu,Yi-Heng Li,Wei-Chuan Tsai,et a1. Prognostic value andthe chases 0f plasmalevels 0f secretory typeII phospholipaseA2 in patients with coronary arterydisease undergoing percutaneous coronary intervention.EHJ,2003,20:l824-1832.
[36]Iro Hoshida , Masami , Nishino , et al . A persistent increase in C - reactive protein is a risk factor for restenosis in patients with stable nagina who are not receiving statins[J]. Atherosclerosis ,2004 ,173 :285 - 290.
[37]付银环,袁伟东,张丹等. 氟伐他汀对冠状动脉支架置人术所致高敏 C 反应蛋白干预作用的研究[J]. 中华临床医学研究杂志,2007,12(12)23:3132-3133.
[38]苏华,杜优优,潘宏伟. 阿托伐他汀对急性冠状动脉综合征患者 PCI 术后炎症因子的影响[J].临床荟萃,2007,2(22)3:155-158.)
[39]Falk E,shall PK,Fuster V.Coronary plaque disruption.Circulation,l995.92:657—671.
[40]Jan J,Re bbert J.Type II secretory phospholipase A2:The emerging role Of biochemical markes 0f plaque inflammation Editoria1.EHJ,2003,20:l804—1806.
[41]Korotaeva AA,Pmvatomv SI,Samoflova EV,et a1.Sennnlevel 0f Secre一 tory phospholipaseA2(sPLA2)as apredictor of restenosis after coronary angioplasty.Ter Arkh,2002,74(4):12～l5.
[42]刘晓桥,吴强,刘志琴等. 不同临床及血管病变类型的患者行介入治疗术后hs—CRP 变化规律探讨[J].中国医师进修杂志.2007,5(30)5:11-13.
[43]Saleh N,Svane B,Velander M,et al.C-reactive protein and myocardil infarction during percutaneous coronary intervention [J].J Intern Med.2004,255(1):33-39.
[44]Gogo P,Schneider D,Watkins M,et al.Systemic inflammation After Drug-Eluting Stent Placement[J].Journal of Thrombosis and Thrombolysis.2005,19(2)87-92.)
[45]Entmen ML,Smith CW.Post reperfusion inflamm action:a model for reaction to injury in cardiovascular disease[J].Cardiovasc Res,1994,38:1303-1311.
[46]Panse N,Brett S,Panse P,et al.Multiple plaque morphologies in a single coronary artery : insights from volumetric intravascular unltrasound.Cather Cardiovasc Interv.2004,61:376-380.
[47]陈文强,张立,张梅,等.血管内超声和病理学分析对比研究动脉粥样硬化兔不稳定斑块的破裂和血栓形成[J].中华超声影像学杂志,2004,I3(10):777—779.
[48]Libby P . Ridker PM . Maseri A , Inflammation and atherosclerosis.Circulation.2002.105 (9)1135)
[49]Ballantyne CM,Hoogeveen RC,Bang H,et al.Lipoprotein- associated phospholipase A2,high-sensitivity C-reactive protein,and risk for incident coronary deart disease in middle-aged men and women in the Atherosclerosis Risk in Communities(ARIC)study[J]. Circulation,2004,109:837-842.
[50]Int J Emerg and Crit Care Med,March,2007 Vo1.4,No.2:1757-1758.
[1] Six DA,Dennis EA.The expanding superfamily of phospholipase A2 enzymes:cl- assification and characterization[J].Biochim Biophys Acta ,2000,1488(1-2):1-19.
[2] 陈莉延.磷脂酶A2的研究进展[J].国外医学生理、病理科学与临床分册,2000,20(6):473-476.
[3] Hansson GK. Inflammation,atherosclerosis,and coronary artery disease [J].N Engl J Med,2005,352:1685-1695.
[4] Sanchez-Quesada JL, Benitez S, Ordonez-Llanos J.Electronegative low- density lipoprotein[J].Curr Opin Lipidol,2004,15:329-335.
[5] Benitez S,Benitez S,Villegas V,et al.Impaired binding affinty of electronegative low-density lipoprotein (LDL) to the LDL receptor is related to nonesterified fatty acids and lysophosphatidylcholine content[J].Biochemistry,2004,43: 158 63-15872.
[6] Benitez S,Camacho M,Arcelus R,et al.Increased lysophosphatidyl chol- ine and nonesterified fatty acid content in LDL induces chemokine release in endothelial cells. Relationship with electronegative LDL [J].Atherosclerosis,2004,177:299-305.
[7] Theilmeier G,de Geest B,van Veldhoven PP,et al.HDL-associated PAF-AH reduces endothelial adhesiveness in apoE-/-mice[J].FASEB J,2000,14: 2032-2039.
[8] Quarck R,de Geest B,Stengel D,et al. Adenovirus-mediated gene transf- er of human platelet-activating factor-acetylhy drolase prevents injury-induced neointima formation and reduces spontaneous athero- sclerosis in apolipoprotein E deficientmice[J].Circulation,2001, 103:2495-2500.
[9] Blankenberg S,Stengel D,Rupprecht HJ,et al.Plasma PAF- acetylhydr- olase in patients with coronary artery disease: results of a cross-sectional analysis[J].J Lipid Res,2003,44:1381-1386.
[10] Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis[J].Arterioscler Thromb Vasc Biol, 2006:26(11):2523-2529.
[11]Carpenter KL,Dennis IF,Challis IR,et al.Inhibition of lipoprotein- associated phospholipase A2 diminishes the death-inducing effects of oxidised LDL on human monocytemacrophages[J].FEBS Lett,2001,505: 357-363.
[12] Macphee CH .Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target[J]. Curr Opin Pharmacol,2001,1:121-125.
[13] Tsimihodimos V,Kakafika A,Tambaki AP,et al.Fenofibrate induces HDL- associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins [J].J Lipid Res, 2003, 44:927-934.
[14] Walter MF,Jacob RF,Jeffers B,et al.Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study[J].J Am Coll Cardiol,2004,44:1996-2002.
[15] Ballantyne CM,Hoogeveen RC,Bang H,et al.Lipoprotein-associated phospholipase A2,high- sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study[J].Circulation, 2004,109:837-842.
[16] Ballantyne C,Hoogeveen RC,Bang H,et al.Lipoprotein associated pho- spholipase A2, high-sensitivity C-reactive protein, and risk for ischemic stroke in middle- aged men and women in the Atherosclerosis Risk in Communities Study[J].Circulation,2004,110:III-641.
[17] Koenig W,Khuseyinova N,Lowel H,et al.Lipoprotein-associated phosph- olipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany[J].Circulation,2004,110:1903-1908.
[18] Oei HHS,van der Meer I,Hofman A, et al.Lipoprotein-associated phospholipase A2 is associated with risk of coronary heart disease and stroke: The Rotterdam Study[J]. Circulation,2005,111:570-575.
[19] Kolodgie FD,Burke AP,Taye A, et al.Lipoprotein-associated phosp- holipase A2 is highly expressed in macrophages of coronary lesions prone to rupture[J].Circulation,2004,110(suppl III):246-247.
[20] 刘甲兴,郑 兴.脂蛋白相关性磷脂酶 A2 活性能反应冠状动脉粥样硬化病变程度[J].第二军医大学学报,2006,27(4):391-395.
[21] 于 路,姜文兵.冠心病患者分泌型磷脂酶 A2 的变化及其与白细胞介素 8、溶血磷脂酸的关系[J].中华心血管病杂志,2006,34(9):812-815.
[22] Yang EH, McConnell JP, Lennon RJ,et al.Lipoprotein-associated phospholipase A2 is an independent marker for coronary endothelial dysfunction in humans artherioscler[J].Thromb Vasc Biol,2006,26: 106-111.
[23] Khuseyinova N ,Imhof A, Rothenbacher D,et al. Association between Lp-PLA2 and coronary artery disease: focus on its relationship with lipoproteins and markers of inflammation and hemostasis[J].Athero- sclerosis,2005,182:181-188.
[24] Iribarren C,Gross MD, Darbinian JA,et al.Association of lipoprotein- associated phospholipase A2 mass and activity with calcified coronary plaque in young adults. The CARDIA Study[J]. Arterioscler Thromb Vasc Biol,2005,25: 216-221.
[25] Brilakis ES,McConnell JP,Lennon RJ,et al.Association of lipopro-tein-associated phospholipase A2 levels with coronary artery disease risk factors,angiographic coronary artery disease, and major adverse events at follow-up[J].Eur Heart J,2005,26:137-144.
[26] Garza CA, Montori VM, McConnell JP,et al. Association between lipoprotein- associated phospholipase A2 and cardiovascular disease: a systematic review[J]. Mayo Clin Proceedings,2007,82(2):159-165.
[2] Danesh J,Wheeler JR,Hirschfield GM,et al.C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart diseasa[J].N Engl J Med.2004,350:1387-1397.
[3] Ridker PM,Hennekens CH,Buring JE,et al.C-reactive protein and other markers of inflammation in the cardiovascular disease in Women[J].N Engl J Med.2003,342:836-843.
[4] 陈国伟,郑宗锷,主编.现代心脏内科学.第二版.湖南长沙:湖南科学技术出版社,2002.1037-1038.
[5] YANG Ping,HANG Yonglun,WEN Xianyong,et al.Clinical Significance of Inflammatory Markers in Patients with Coronary Heart Disease[J].J Med Theor&Prac Vo1.20,No.1,Jan2007:9-10.
[6] Six DA,Dennis EA.The expanding superfamily of phospholipase A2 enzymes:classification and characterization[J].Biochim Biophys Acta ,2000,1488(1-2):1-19.
[7] Kolodgie FD,Burke AP,Taye A, et al.Lipoprotein- associated phospholipase A2 is highly expressed in macrophages of coronary lesions prone to rupture[J].Circulation,2004,110 (suppl III):246-247.
[8] Macphee CH .Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target[J].Curr Opin Pharmacol,2001, 1:121-125.
[9] 陈莉延.磷脂酶 A2 的研究进展[J].国外医学生理、病理科学与临床册,2000,20(6):473-476.
[10] 陆青,杨海敏.全身 CRP 测定仪及其试剂的评估[J].上海医学检验杂志,1999,14(5):268– 269.
[11]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.慢性稳定性心绞痛诊断与治疗指南[J].中华心血管病杂志,2007,35(3)3:195-206.
[12]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.不稳定型心绞痛诊断和治疗建议[J].中华心血管病杂志,2000,28(6):409-412.
[13]中华医学会心血管病学分会,中华心血管病杂志编辑委员会,中国循环杂志编辑委员会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,12(29)12:710-725.
[14] 葛均波.血管内超声波多普勒学.北京:人民卫生出版社,2000:114.
[15] Shah PK. Mechanisms of plaque vulnerability and rupture[J].J Am Coil Cardiol,2003,41(4 Suppl S):15S--22S.
[16] 杨立明,赵宝春.不同类型炎症C一反应蛋白水平的差异与冠心病的关系[J]. 中国煤炭工业医学杂志,2007,3(1O),3:275-276.
[17] Etri T,Kovan en,Markku O,et a1.Secretory Group11 PhospholipaseA2,A newly Recognized Acute — Phase Reactant With a Role in Atherogenesis Editoria1.Circulation Research,2O00,86:610.
[18] Kimura-Matsumoto M, Ishikawa Y, Komiyama K,et al. Expression of secretory phospholipase A2s in human atherosclerosis development. Atherosclerosis. 2007,Mar:10. [Epub ahead of print]
[19] Ghesquiere S,Gijbels M,Anthonsen M,van Gorp P,van der Made I, Johansen B,et al.Macrophage2specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition[J].J Lipid Res,2005,46(2):201-210.
[20] Hurt-Camejo E ,Camejo G,Sartipy P.Phospholipase A2 and small,dense low density lipoprotein[J].Curr Opin Lipidol,2000,11(5):465-471.
[21] 于路,傅国胜,姜文兵等.冠心病患者分泌型磷脂酶 A2 与冠状动脉病变积分及动脉硬化指数的相关性[J].中国介入心脏病学杂志,2007,2(15):31-33.
[22] Niessen H , Krijnen P , Visser C , Meijer C , Eric Hack C. Type II secretory phospholipase A2 in cardiovascular disease : a mediator in atherosclerosis and ischemic damage to cardiomyocytes[J]. Cardiovasc Res,2003,60(1):68-77.
[23] 于路,姜文兵,傅国胜等.冠心病患者分泌型磷脂酶 A2 的变化及其高敏 C反应蛋白的关系[J].中国动脉硬化杂志,2006,14(10):884-886.
[24] Ziad Mallat, Joelle Benessiano, Tabassome Simon,et al. Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women The EPIC-NORFOLK Study[J].Arterioscler Thromb Vasc Biol. 2007;27:1177 -1183.
[25] Messer J V.C-reactive protein and cardiovascular disease[J]. Circul ation,2006, 114:253-254.
[26] 马腾,吴继雄,孙昕. 血清 C-反应蛋白、可溶性 CD40 配体、基质金属蛋白酶-2 水平与冠心病的相关性[J]. 临床心血管病杂志.2007,3(23)3:170-173.)
[27] Zwaka TP,Hombach V,Torzewski J.C—reactive protein mediated low density lipoprotein uptake by macrophages : implications for atherosclerosis [J].Circulation;2001,103(6):1194—1197.
[28] Nakagomi A , Freedman SB , Geczy CL . Interferongamma and lipopolysaccharide potentiate monocyte tissue factor induction by C —reactive protein:relationship with age,sex,and hormone replacement treatment[J].Circulation,2000,101(10):1784—1791.
[29] Yasojima K,Schwab C,Mcgeer EG,et a1.Generation of C—reactive protein and complement components in atherosclerotic plaques[J].Am J Pathol,2001,158(7):1039—1049.)
[30] Person GR.Pettemson T.Ohlsson 0.Renvert S.High—sensitivity serun C- —reactive protein levels in subjects with or without myocardialinfarction or periodontitis,[J].J Clin Periodontol.20O5.32(3):219—224.
[31]Taniguchi H.Momiyama Y.Ohmofi R.Yonemura A.Yanmshita T.Tamai S.et a1.Associations of plasma C-reactive protein leveh with the presence and extent of coronary stenosis in patiens with stable coronary artery disease [J]. Atheroscerosis.2OO5.178(1):173-l77.)
[32]齐藤宪祜.超敏-CRP(hs-CRP)在临床的新应用[G].第五届中日临床技术研讨 会论文汇编,2002,10:30-31.
[33]郑刚,张承中.高敏 C 反应蛋白与急性冠状动脉综合症相关的临床证据[J].中国动脉硬化杂志,2003,11(7):691-694.
[34]Ahmed JM,Mintz GS,Weissman NJ,et a1.Mechanism of lumen enlargement during intracoronary stent implantation:an intravascular ultrasound study[J].Circulation,2000,102(1):7210
[35]Ping-YenLiu,Yi-Heng Li,Wei-Chuan Tsai,et a1. Prognostic value andthe chases 0f plasmalevels 0f secretory typeII phospholipaseA2 in patients with coronary arterydisease undergoing percutaneous coronary intervention.EHJ,2003,20:l824-1832.
[36]Iro Hoshida , Masami , Nishino , et al . A persistent increase in C - reactive protein is a risk factor for restenosis in patients with stable nagina who are not receiving statins[J]. Atherosclerosis ,2004 ,173 :285 - 290.
[37]付银环,袁伟东,张丹等. 氟伐他汀对冠状动脉支架置人术所致高敏 C 反应蛋白干预作用的研究[J]. 中华临床医学研究杂志,2007,12(12)23:3132-3133.
[38]苏华,杜优优,潘宏伟. 阿托伐他汀对急性冠状动脉综合征患者 PCI 术后炎症因子的影响[J].临床荟萃,2007,2(22)3:155-158.)
[39]Falk E,shall PK,Fuster V.Coronary plaque disruption.Circulation,l995.92:657—671.
[40]Jan J,Re bbert J.Type II secretory phospholipase A2:The emerging role Of biochemical markes 0f plaque inflammation Editoria1.EHJ,2003,20:l804—1806.
[41]Korotaeva AA,Pmvatomv SI,Samoflova EV,et a1.Sennnlevel 0f Secre一 tory phospholipaseA2(sPLA2)as apredictor of restenosis after coronary angioplasty.Ter Arkh,2002,74(4):12～l5.
[42]刘晓桥,吴强,刘志琴等. 不同临床及血管病变类型的患者行介入治疗术后hs—CRP 变化规律探讨[J].中国医师进修杂志.2007,5(30)5:11-13.
[43]Saleh N,Svane B,Velander M,et al.C-reactive protein and myocardil infarction during percutaneous coronary intervention [J].J Intern Med.2004,255(1):33-39.
[44]Gogo P,Schneider D,Watkins M,et al.Systemic inflammation After Drug-Eluting Stent Placement[J].Journal of Thrombosis and Thrombolysis.2005,19(2)87-92.)
[45]Entmen ML,Smith CW.Post reperfusion inflamm action:a model for reaction to injury in cardiovascular disease[J].Cardiovasc Res,1994,38:1303-1311.
[46]Panse N,Brett S,Panse P,et al.Multiple plaque morphologies in a single coronary artery : insights from volumetric intravascular unltrasound.Cather Cardiovasc Interv.2004,61:376-380.
[47]陈文强,张立,张梅,等.血管内超声和病理学分析对比研究动脉粥样硬化兔不稳定斑块的破裂和血栓形成[J].中华超声影像学杂志,2004,I3(10):777—779.
[48]Libby P . Ridker PM . Maseri A , Inflammation and atherosclerosis.Circulation.2002.105 (9)1135)
[49]Ballantyne CM,Hoogeveen RC,Bang H,et al.Lipoprotein- associated phospholipase A2,high-sensitivity C-reactive protein,and risk for incident coronary deart disease in middle-aged men and women in the Atherosclerosis Risk in Communities(ARIC)study[J]. Circulation,2004,109:837-842.
[50]Int J Emerg and Crit Care Med,March,2007 Vo1.4,No.2:1757-1758.
[1] Six DA,Dennis EA.The expanding superfamily of phospholipase A2 enzymes:cl- assification and characterization[J].Biochim Biophys Acta ,2000,1488(1-2):1-19.
[2] 陈莉延.磷脂酶A2的研究进展[J].国外医学生理、病理科学与临床分册,2000,20(6):473-476.
[3] Hansson GK. Inflammation,atherosclerosis,and coronary artery disease [J].N Engl J Med,2005,352:1685-1695.
[4] Sanchez-Quesada JL, Benitez S, Ordonez-Llanos J.Electronegative low- density lipoprotein[J].Curr Opin Lipidol,2004,15:329-335.
[5] Benitez S,Benitez S,Villegas V,et al.Impaired binding affinty of electronegative low-density lipoprotein (LDL) to the LDL receptor is related to nonesterified fatty acids and lysophosphatidylcholine content[J].Biochemistry,2004,43: 158 63-15872.
[6] Benitez S,Camacho M,Arcelus R,et al.Increased lysophosphatidyl chol- ine and nonesterified fatty acid content in LDL induces chemokine release in endothelial cells. Relationship with electronegative LDL [J].Atherosclerosis,2004,177:299-305.
[7] Theilmeier G,de Geest B,van Veldhoven PP,et al.HDL-associated PAF-AH reduces endothelial adhesiveness in apoE-/-mice[J].FASEB J,2000,14: 2032-2039.
[8] Quarck R,de Geest B,Stengel D,et al. Adenovirus-mediated gene transf- er of human platelet-activating factor-acetylhy drolase prevents injury-induced neointima formation and reduces spontaneous athero- sclerosis in apolipoprotein E deficientmice[J].Circulation,2001, 103:2495-2500.
[9] Blankenberg S,Stengel D,Rupprecht HJ,et al.Plasma PAF- acetylhydr- olase in patients with coronary artery disease: results of a cross-sectional analysis[J].J Lipid Res,2003,44:1381-1386.
[10] Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis[J].Arterioscler Thromb Vasc Biol, 2006:26(11):2523-2529.
[11]Carpenter KL,Dennis IF,Challis IR,et al.Inhibition of lipoprotein- associated phospholipase A2 diminishes the death-inducing effects of oxidised LDL on human monocytemacrophages[J].FEBS Lett,2001,505: 357-363.
[12] Macphee CH .Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target[J]. Curr Opin Pharmacol,2001,1:121-125.
[13] Tsimihodimos V,Kakafika A,Tambaki AP,et al.Fenofibrate induces HDL- associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins [J].J Lipid Res, 2003, 44:927-934.
[14] Walter MF,Jacob RF,Jeffers B,et al.Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study[J].J Am Coll Cardiol,2004,44:1996-2002.
[15] Ballantyne CM,Hoogeveen RC,Bang H,et al.Lipoprotein-associated phospholipase A2,high- sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study[J].Circulation, 2004,109:837-842.
[16] Ballantyne C,Hoogeveen RC,Bang H,et al.Lipoprotein associated pho- spholipase A2, high-sensitivity C-reactive protein, and risk for ischemic stroke in middle- aged men and women in the Atherosclerosis Risk in Communities Study[J].Circulation,2004,110:III-641.
[17] Koenig W,Khuseyinova N,Lowel H,et al.Lipoprotein-associated phosph- olipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany[J].Circulation,2004,110:1903-1908.
[18] Oei HHS,van der Meer I,Hofman A, et al.Lipoprotein-associated phospholipase A2 is associated with risk of coronary heart disease and stroke: The Rotterdam Study[J]. Circulation,2005,111:570-575.
[19] Kolodgie FD,Burke AP,Taye A, et al.Lipoprotein-associated phosp- holipase A2 is highly expressed in macrophages of coronary lesions prone to rupture[J].Circulation,2004,110(suppl III):246-247.
[20] 刘甲兴,郑 兴.脂蛋白相关性磷脂酶 A2 活性能反应冠状动脉粥样硬化病变程度[J].第二军医大学学报,2006,27(4):391-395.
[21] 于 路,姜文兵.冠心病患者分泌型磷脂酶 A2 的变化及其与白细胞介素 8、溶血磷脂酸的关系[J].中华心血管病杂志,2006,34(9):812-815.
[22] Yang EH, McConnell JP, Lennon RJ,et al.Lipoprotein-associated phospholipase A2 is an independent marker for coronary endothelial dysfunction in humans artherioscler[J].Thromb Vasc Biol,2006,26: 106-111.
[23] Khuseyinova N ,Imhof A, Rothenbacher D,et al. Association between Lp-PLA2 and coronary artery disease: focus on its relationship with lipoproteins and markers of inflammation and hemostasis[J].Athero- sclerosis,2005,182:181-188.
[24] Iribarren C,Gross MD, Darbinian JA,et al.Association of lipoprotein- associated phospholipase A2 mass and activity with calcified coronary plaque in young adults. The CARDIA Study[J]. Arterioscler Thromb Vasc Biol,2005,25: 216-221.
[25] Brilakis ES,McConnell JP,Lennon RJ,et al.Association of lipopro-tein-associated phospholipase A2 levels with coronary artery disease risk factors,angiographic coronary artery disease, and major adverse events at follow-up[J].Eur Heart J,2005,26:137-144.
[26] Garza CA, Montori VM, McConnell JP,et al. Association between lipoprotein- associated phospholipase A2 and cardiovascular disease: a systematic review[J]. Mayo Clin Proceedings,2007,82(2):159-165.