摘要
第一部分斑块纤维帽厚度与血浆炎症标志物对冠心病患者不稳定斑块的预测阈值研究
背景急性冠脉综合症的发病与动脉粥样硬化斑块的不稳定性密切相关,而斑块纤维帽厚度是决定斑块稳定性的关键因素之一,通常所指的易损斑块即为纤维帽厚度小于65μm;血管内光学相干断层成像技术为我们提供了高分辨率(~10μm),获得组织原位横截面图像的检测手段,光学相干断层成像技术的出现是我们检测不稳定斑块纤维帽厚度成为可能。临床心血管事件与某些炎症标记物水平同样密不可分;大量研究证实,外周血中炎症标志物水平具有预测心血管事件的价值;然而,斑块纤维帽厚度与血浆炎症标志物对冠心病患者易损斑块的预测阈值大小及其相关性尚未见报道。
目的评价斑块纤维帽厚度与血浆炎症因子的相关性,初步探讨两者预测冠心病患者不稳定斑块的阈值。
方法及结果将急性心肌梗死、不稳定性心绞痛、稳定性心绞痛及胸痛综合症患者纳入研究对象,进行对照研究。冠状动脉粥样硬化斑块纤维帽厚度采用血管内光学相干断层成像技术进行检测;通过酶联免疫吸附试验检测入选者血浆中超敏C反应蛋白、白介素-18及肿瘤坏死因子α血浆表达水平。随着冠脉事件风险增加,冠脉纤维帽厚度变薄,同样,患者血浆超敏C反应蛋白、白介素-18及肿瘤坏死因子α水平亦显著增加。冠状动脉纤维帽厚度与血浆炎症因子水平显著相关;当冠状动脉粥样硬化斑块纤维帽厚度小于65μm时,上述血浆炎症因子表达水平分别超出下述阈值水平:hs-CRP 0.75 mg/L,IL-18 75μg/L and TNF-α35μg/L,两者之间显著相关。
结论由上可知,hs-CRP 0.75 mg/L,IL-18 75μg/L and TNF-α35μg/L可作为有效地甄别阈值用来预测动脉粥样硬化斑块的稳定性;为今后临床实践提供了一种简单有效地甄别不稳定斑块的无创性诊疗工具。
第二部分冠心病患者炎症因子表达水平变化的相关性研究
背景许多研究发现炎症反应不但在动脉粥样硬化的发生发展过程中起到了十分重要的作用,而且炎症反应在动脉粥样硬化斑块的不稳定过程中扮演了非常关键的角色,炎症同时也是动脉血栓形成各阶段的特征,是斑块形成和急性破裂而导致动脉闭塞和梗死的关键病理生理学机制,这些发现使得炎症因子与冠心病关系开始日益受到人们的重视。因此,明确冠心病患者血浆炎症因子水平及冠心病与炎症因子的相关性可能有助于危险冠心病患者的早期甄别。
目的探讨冠心病患者不同临床阶段,白细胞介素-10(IL-10),白细胞介素-17(IL-17),白细胞介素-18(IL-18)、超敏C反应蛋白(hs-CRP)及肿瘤坏死因子-α(TNF-α)在血浆中的表达水平的变化,并初步明确两者的相关性。
方法将急性心肌梗死、不稳定性心绞痛、稳定性心绞痛及胸痛综合症患者纳入研究对象,进行对照研究。采用酶联免疫双抗体夹心法(ELISA)对160例冠心病人(急性心梗50例,不稳定心绞痛68例,稳定性心绞痛42例和40例胸痛综合症患者血浆中IL-10、IL-17、IL-18、hs-CRP及TNF-α的水平进行检测。
结果随着冠心病临床事件风险增加,冠心病患者血浆IL-17、IL-18、hs-CRP及TNF-α的水平均显著增加,IL-10血浆水平在冠心病患者均表达增加,与胸痛综合症组相比具有显著统计学差异,但并未表现出随临床事件风险增加而表达上升的趋势,在稳定型心绞痛组其表达量反高于不稳定心绞痛组,提示在稳定斑块向不稳定斑块进展的时候,可能有其他机制抑制IL-10的表达,但其具体机制尚待进一步明确。
结论IL-10、IL-17、IL-18、hs-CRP及TNF-α等炎症因子可能共同参与了动脉粥样硬化发生、发展和演变的过程,其血浆水平可作为判断冠心病患者病情,筛选高危患者的指标之一。
第三部分C-myc及PCNA对动脉粥样硬化斑块中血管平滑肌细胞增殖的影响
背景动脉粥样硬化由脂质条纹进展至纤维酯性病变的过程中,内膜中的平滑肌细胞分裂,中膜的部分平滑肌细胞迁移至内膜;同时,平滑肌细胞分泌大量细胞外基质,促进细胞外基质在进展期动脉粥样硬化斑块处积聚。另外,平滑肌细胞的凋亡也参与了动脉粥样斑块复杂的发展过程。斑块纤维帽变薄即是平滑肌细胞增殖与凋亡失衡的结果。如何抑制血管平滑肌细胞增殖对延缓动脉粥样硬化进展意义重大。川芎是常用治疗动脉粥样硬化中药复方的主要成分,研究认为,川芎主要活性成分——川芎嗪可能具有抑制平滑肌细胞增殖的作用,但具体机制不明。C-myc原癌基因的表达产物c-myc蛋白作为一个“获能因子”可促进与VSMC增殖相关基因的开放,产生大量生长因子样物质,使VSMC进入增殖状态。细胞增殖核抗原(proliferating cell nuclearantigen,PCNA)是DNA复制、细胞周期及分裂过程中信号传导的关键一环,当VSMC细胞增殖旺盛时,其基因表达迅速增加。因此,川芎嗪抑制平滑肌细胞增殖的机制及C-myc及PCNA在平滑肌细胞增殖过程中的作用亟待阐明。
目的观察c-myc和PCNA的反义寡核苷酸对原代培养VSMC增殖的抑制作用。同时对不同浓度川芎嗪抑制VSMC增殖的作用进行了研究,阐明其分子生物学作用基础。
方法选择4-8代培养的鼠胸主动脉血管平滑肌细胞作为研究对象:分对照组、PCNA ODNs组和c-myc ODNs组进行对照研究,ODNs工作浓度均为1:50。选择细胞计数、MTT法、~3H-TdR掺入法探讨ODNs对VSMC增殖的抑制作用;并以免疫组织化学法检测PCNA和c-myc ODNs转入VSMC及抑制相应PCNA和c-myc基因表达的情况。在观察川芎嗪作用中:分对照组(Ⅰ组)、川芎嗪50μg/ml(Ⅱ组)、100μg/ml(Ⅲ组)、200μg/ml(Ⅳ组);采用细胞计数、VSMC对~3H-TdR的摄取量和MTT法测OD_(570)值三种方法,探讨川芎嗪对VSMC生长的影响,通过检测PCNA(细胞增殖核抗原)和C-myc二种基因的表达来探讨川芎嗪抑制VSMC增殖的作用机理。
结果细胞计数法、MTT法和~3H-TdR摄取量检测法均显示PCNA和c-myc ODNs对VSMC的增殖有抑制作用,与对照组相比较均有显著性差异(p<0.05);免疫组织化学法显示PCNA和c-myc ODNs成功地转入了VSMC中并明显抑制相应基因的表达,与对照组相比较差异显著(P<0.05);细胞计数、~3H-TdR摄取量检测及MTT法均显示川芎嗪对VSMC的增殖有抑制作用,且呈剂量依赖性,200μg/ml川芎嗪作用72小时对VSMC的增殖抑制作用最强,组间相比较均具有显著意义(P<0.05);川芎嗪抑制VSMC增殖过程中PCNA、C-myc的表达明显降低,且与川芎嗪的作用浓度相关,组间相比较均具有显著性差异(P<0.05)。
结论PCNA和c-myc基因在VSMC的增殖过程中起重要作用,PCNA和c-mycODNs导入VSMC后可成功抑制相应基因的表达,从而抑制VSMC的增殖;川芎嗪对鼠原代培养的VSMC的增殖确有明显抑制作用,并呈剂量依赖性;川芎嗪是通过影响与VSMC增殖有密切关系的基因PCNA、C-myc的表达发挥该作用;为深入挖掘祖国医学宝库治疗AS提供了理论依据,也为临床应用提供了重要依据
PartⅠ
Study the threshold of the thickness of fibroma and the level of serum inflammation markers in CAD patients with unstable plaques
Background There are robust correlations between acute coronary syndrome and the stability of atherosclerotic plaque.However,the thickness of cap fibroatheroma is the critical factor affects the stability of atherosclerotic plaque.A vulnerable plaque was defined as the thin cap fibroatheroma(TCFA,<65μm).Intravascular optical coherence tomography(OCT) provides high-resolution(~10μm),cross-sectional images of tissue in situ.The resolution of OCT is appropriate for measuring the cap thickness of a vulnerable plaque.There are robust correlations between clinical cardiovascular events and the leverls of serum inflammatory markers.Data from large-scale population-based studies have demonstrated that increased circulating levels of numerous markers of inflammation predict future cardiovascular events.The cut-off value and the correlation of the thickness of cap fibroatheroma and the levels of inflammatory markers are still need to be clarified.
Aims To evaluate the correlation between fibrous cap thickness and levels of plasma inflammatory factors,and search those thresholds for predicting vulnerable plaques in patients with coronary artery diseases.
Methods and results A comparative study was performed in patients with acute myocardial infarct(AMI),unstable angina pectoris(UAP),stable angina pectoris(SAP) and chest pain syndrome(CPS).Intravascular optical coherence tomography was used to measure the fibrous cap thickness of coronary artery atherosclerotic plaques.Enzyme linked immunosorbent assay was used to detect plasma levels of highly sensitive C-reacting proteins(hs-CRP),interleukin 18(IL-18) and tumor necrosis factor alpha(TNF-α).With increases of coronary artery event risks,plaque fibrous cap thickness decreased and plasma hs-CRP,IL-18 and TNF-αlevels increased considerably(P<0.05).There were significant correlations between fibrous cap thickness and plasma levels of inflammatory factors (P<0.05).Cap thickness<65βm correlated with threshold levels of plasma inflammatory factors as follows:hs-CRP 0.75 mg/L,IL-18 75μg/L and TNF-α35μg/L.
Conclusion Results show that cut-off value of hs-CRP≥0.75mg/L,IL-18<75μg/L and TNF-α≥35μg/L could be the threshold to predict instability of atherosclerotic plaques. It may provide an easy way to identify vulnerable patients in future clinical practice.
PartⅡ
Correlation between inflammatory factors and different state of coronary artery disease
Background Abundant data link hypercholesterolaemia to atherogenesis.However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation.Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis,and malfunction of inflammatory mediators mutes atheroma formation.Moreover,inflammatory pathways promote thrombosis,a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes.Dependend these data,the new appreciation of the correlation between inflammation and coronary artery disease has been paid close attention to.Therefore, unrevalling the levels of serum inflammatory factors and identifying the correlation between inflammatory factors and different state of coronary artery disease may eventually furnish the discrimination of dangerous CAD patients.
Objective To detecte the diversity of serum levels of interleukin-10(IL-10), intedeukin-17(IL-17),interleukin-18(IL-18),C reactive protein(CRP) and TNF-αin the process of coronary artery disease(CAD).and to identify the correlation between inflammatory factors and different state of CAD.
Methods The levels of plasma IL-10,IL-17,IL-18,hs-CRP and TNF-αin 160 patients(AMI50,UAP68,and SAP42) with CAD and 40 CPS were determined by enzyme linked immunoadsorbent assay(ELISA).
Results The plasma levels of IL-17,IL-18,hs-CRP and TNF-αin patients with CAD wre increased significantly than that in CPS patients(P<0.05).The concentration of IL-10 in patients with CAD was increased significantly than that in CPS patients(P<0.05), however,the serum level of IL-10 in UAP patients was lower than that in SAP group,there may be some mechanism need to be unrevlled to clarify this phenomenon.
Conclutiou The findings suggest that IL-10,IL-17,IL-18,hs-CRP and TNF-αmay co-participate the pathogenesis and progression of CAD.The serum levels of IL-10,IL-17, IL-18,hs-CRP and TNF-αwill contribute to the assement of the pathogenetic condition with CAD.The levels of these inflammatory markers could be one of the references in discriminating the dangerous patients.
PartⅢ
Effects of the c-myc and PCNA on the multiplication of VSMC
Background Smooth muscle cells in the intima divide,other smooth muscle cells that migrate into the intima from the media.Smooth muscle cells can then divide and elaborate extracellular matrix,promoting extracellular matrix accumulation in the growing atherosclerotic plaque.In this manner,the fatty streak can evolve into a fibrofatty lesion.In addition to smooth muscle cell replication,death of these cells can also participate in the complication of the atherosclerotic plaque.Thin cap fibroatheroma in the growing atherosclerotic plaque probably results from a tug-of-war between cell replication and cell death.Thus,inhibiting the multiplication of VSMC may be important to retard the development of atherosclerosis.Chuanxiong is the major component of general complex prescription of traditional Chinese herbal in treating atherosclerosis.Some data indicated that chuanxiongzine,the major active ingredient,may inhibit the proliferation of VSMC, however,the mechanism of this effectiveness is still unkown.C-myc protein as the expression product of c-myc proto-oncogene has been shown to be a "compentence factor", which could promote the related gene patency,brings about a great deal of GH-like substance,precipitate VSMC into vegetative state.PCNA is the critical link of signal conduction during the process of DNA duplication,cell cycle and fission.The VSMC gene expression would increase quickly,when the cell proliferate vigorously.Therefore,the mechanism of chuanxiongzine in inhibiting the proliferation of VSMC and the role of c-myc and PCNA in this process need to be unrevelled.
Objective To study the depressive effect of the antisense oligonuceotides(ASODN) of c-myc and proliferating cell nuclear antigen(PCNA) on the proliferation of VSMC. Detecting the inhibitory effect of chuanxiongzine on vascular smooth muscle cell(VSMC) proliferation and exploring its molecular biology basis.
Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4~8 generation as research object.The objects were divided into three groups to carry out control study: control group;PCNA ASODN group and c-myc ASODN group.The ASODNs' working concentration all were 1:50.The depressive effect of ASODN on VSMC proliferation was investigated by cell counting,MTT and ~3H-TdR incorporation assay;PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC.Taking the VSMC obtained from rat aorta thoracalis cultured 4~8 generation as research object.The objects were divided into four groups to carry out control study:(Ⅰ) control group,(Ⅱ) chuanxiongzine(50μg/ml) group,(Ⅲ) chuanxiongzine(100μg/ml) group and(Ⅳ) chuanxiongzine(200μg/ml) group.The inhibitory effect of chuanxiongzine on VSMC proliferation was investigated by cell counting,MTT and ~3H-TdR incorporation assay.In order to illuminate the molecular biology mechanism of chuanxiongzine,the expression of proliferating cell nuclear antigen (PCNA) and c-myc were detected.
Results PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly,compared with control group(P<0.05);Transferring PCNA and c-myc ASODN into VSMC obtained successfully;the corresponding gene was inhibited obviously; compared with control group(P<0.05);Chuanxiongzine could inhibit the proliferation of VSMC significantly in a dose- and time-dependent manner,compared with control group (P<0.05).The expression of PCNA and c-myc were inhibited obviously by chuanxiongzine and was correlated with the concentration of chuanxiongzine(P<0.05).
Conclusion PCNA and c-myc might play a considerable role in the VSMC proliferation process.The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC,and then the proliferation of VSMC was retarded;Chuanxiongzine may play a considerable role in the VSMC proliferation process.The inhibitory effect of chuanxiongzine in a dose- and time-dependent manner could be realized via down regulating the expression of PCNA and c-myc.In this study, great theoretical fundament about Chinese medicine,which is used to treat atherosclerosis (AS),has been obtained.
引文
1.World Health Report 2002:Reducing risks,promoting healthy life.Geneva,World Health Organization,2002.
2.Murray CJL,Lopez AD:The Global Burden of Disease.Cambridge,MA,Harvard School of Public Health,1996.
3.Fuster v Fallon JT,Nemerson Y.Coronary thrombsis.Lancet,1996,348(1):7-10.
4.Depre C,Havaux X,Wijns W.Neovascularization in human coronary atherosclerotic lesions.Cather Cardiovasc Diagn,1996,39:215-220.
5.Nasu K,Tsuchikane E,and Katoh O,et al.Accuracy of in vivo coronary plaque morphology assessment:a validation study of in vivo virtual histology compared with in vitro histopahthology.J Am Coil Cardiol,2006,47(12):2405-2412.
6.Jensen LO,Mintz GS,Carlier SG,et al.Intravascular ultrasound assessment of filbrous cap remnants afer coronary plaque rupture.Am Heart J,2006,152(2):327-332.
7.Ambrose JA,Tannenbaum MA,Alexopoulos D,Hjemdahl-Monsen CE,Leavy J,Weiss M,et al.Angiographic progression of coronary artery disease and the development of myocardial infarction.J Am Coil Cardiol 1988;12:56-62.
8.Kolodgie FD,Burke AP,Farb A,Gold HK,Yuan J,Narula J,et al.The thin-cap fibroatheroma:a type of vulnerable plaque:the major precursor lesion to acute coronary syndromes.Curr Opin Cardiol 2001;16:285-292.
9.Kawasaki M,Bouma BE,Bressner J,et al.Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques.J Am Coil Cardiol,2006,48(1):81-88.
10. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. [J] Circulation, 2002,105(9): 1135-1143.
11. Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844-2850.
12. Geng YJ, Libby P. Progression of atheroma: A struggle between death and procreation. Arterioscler Thromb Vasc Biol. 2002, 22:1370.
13. Nagai R, Suzuki T, Aizawa K, et al. Phenotypic modulation of vascular smooth muscle cells: Dissection of transcriptional regulatory mechanisms. Ann N Y Acad Sci 2001,947:56.
14. Manabe I, Nagai R. Regulation of smooth muscle phenotype. Curr Atheroscler Rep.2003,5:214.
15. Ross R, Glomset JA. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis [J].Science 1973; 180(93): 1332-339.
16. David WM, Muller. The role of proto-oncogene in coronary restenosis [J]. Prog in Cardiovasc Dis. 1997,40:117-128.
17. Zhang YR, Zhang YX, Cao W, et al. Uptake kinetics of 99mTc-MAG3-antisense oligonucleotide to PCNA and effect on gene expression in vascular smooth muscle cells [J]. J Nucl Med. 2005,46(6):1052-8.
1. Burke A P, Farb A, Malcom G T, Liang Y-H, Smialek J, and Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336:1276-82.
2. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135 -43.
3. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science. 1991;254:1178-1181.
4. Tearney GJ, Brezinski ME, Bouma BE, et al. In vivo endoscopic optical biopsy with optical coherence tomography. Science. 1997; 276: 2037-2039.
5. Tearney GJ, Yabushita H, Houser SL, Aretz HT, Jang IK, Schlendorf KH, Kauffman CR, Shishkov M, Halpern EF, Bouma BE. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation.2003;107:113-119.
6. Raffel OC, Tearney GJ, Gauthier DD, Halpern EF, Bouma BE, Jang IK. Relationship between a systemic inflammatory marker, plaque inflammation, and plaque characteristics determined by intravascular optical coherence tomography. Arterioscler Thromb Vasc Biol.2007; 27:1820-1827.
7. Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, Choi KB, Shishkov M,Schlendorf K, Pomerantsev E, Houser SL, Aretz HT, Tearney GJ. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol. 2002; 39:604-609.
8. Grube E, Gerckens U, Buellesfeld L, Fitzgerald P. Intracoronary imaging with optical coherence tomography: a new high-resolution technique providing striking visulaization in the coronary artery. Circulation.2002; 106: 2409-2410.
9. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000; 20:1262-1275.
10. Kolodgie FD, Virmani R, Burke AP, Farb A, Weber DK, Kutys R, Finn AV, Gold HK.Pathologic assessment of the vulnerable human coronary plaque. Heart.2004;90:1385-1391.
11. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the unstable plaque. Prog Cardiovasc Dis.2002; 44:349-356.
12. Shah PK. Mechanisms of plaque vulnerability and rupture. J Am Coll Cardiol.2003;41:15- 22.
13. Yun DD, Alpert JS. Acute coronary syndromes. Cardiology.1997; 88:223-237.
14. Jang IK, Tearney G, Bouma B. Visualization of tissue prolapse between coronary stent struts by optical coherence tomography: comparison with intravascular ultrasound. Circulation.2001; 104:2754.
15. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M,Houser S, Aretz HT, Halpern EF, Bouma BE. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation.2005;111:1551-1555.
16. Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, Choi KB, Shishkov M,Schlendorf K, Pomerantsev E, Houser SL, Aretz HT, Tearney GJ. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography:comparison with intravascular ultrasound. J Am Coll Cardiol.2002; 39: 604-609.
17. Ridker PM , Henneken CH , Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in woman.N Engl J Med.2000;342:836-843.
18. Blankenberg S, Luc G, Ducimetiere P, Arveiler D, Ferrieres J, Amouyel P, Evans A,Cambien F, Tiret L.Interleukin-18 and the risk of coronary heart disease in european men: the prospective epidemiological study of myocardial infarction. Circulation.2003;108:2453-2459.
19. Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, Rupprecht HJ.Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.Circulation. 2002; 106: 24-30.
20. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor -alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation.2000; 101:2149-2153.
1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. [J] Circulation, 2002,105(9): 1135-1143.
2. Stefanadis C, Vavuranakis M, Toutouzas P. Vulnerable plaque: The challenge to identify and treat it. J Interv Cardiol. 2003,16:273.
3. Buffon A, Biasucci LM, Liuzzo G, et al. Widespread coronary inflammation in unstable angia. N Engl J Med. 2002, 347:5.
4. Ridker PM. Clinical application of C-rreactive protein for cardiovascular disease detection and prevention. Circulation. 2003,107:363.
5. Hashmi S, Zeng QT. Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. [J] Coron Artery Dis. 2006 Dec; 17(8):699-706.
6. Okamura H, Komatsu T, Komatsu T. Cloning of a new cytokine that induces IFN-gamma production by T cells. NATURE. 1995, 378/6552: 88-91.
7. Ridker PM, Rifai N , Pfeffer M, et al . Elevation of tumor necrosis factor-alph and increased risk of recurrent coronary events after myocardial infarction. Circulation,2000,101:2149-2153.
8. Willner EL, Tow B, Buhman, KK, et al. Deficiency of ACAT2 prevents atherosclerosis in apolipoprotein E-dificient mice. Proc Natl Acad Sci USA. 2003,100:1262.
9. Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 1992, 258:468.
10. O'Connell BJ, Genest J Jr. High-density lipoproteins and endothelial function.Circulation. 2001,104:1978.
11. Li XA, Titlow WB, Jackson BA, et al. High density lipoprotein binding to scavenger receptor, class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner. J Biol Chem 2002, 277:11058.
12. Oram JF. HDL apolipoproteins and ABCA1: Partners in the removal of excess cellular cholesterol. Arterioscler Thromb Vasc Biol 2003, 23:720.
13. Bodzioch M, Orso E, Klucken J, et al. The gene encoding ATP-bingding cassette transportel is mutated in Tangier disease.Nat Genet 1999,22:347.
14.Lakoski SG,Liu Y,Brosnihan KB,et al.Interleukin-10 concentration and coronary heart disease(CHD) event risk in the estrogen replacement.and atherosclerosis(ERA)study.Atherosclerosis.2008 Mar;197(1):443-447.
15.刘文卫,廖玉华。白细胞介素-18:一种预测冠心病新的重要标记物。临床心血管病杂志[J],2006,22(2):65-66。
16.Mallat Z,Corbaz A,Scoazec A,et al.Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.Circulation.[J]2001 Oct;104(14):1598-1603.
17.de Winter RJ,Fischer JC,de Jongh T,et al.Different time frames for the occurrence of elevated levels of cardiac troponin T and C-reactive protein in patients with acute myocardial infarction.[J]Clin Chem Lab Med.2000 Nov;38(11):1151-3.
18.Pasceri V,Cheng JS,Willerson JT,Yeh ET,et al.Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.[J]Circulation.2001 May 29;103(21):2531-4.
19.Zwaka TP,Hombach V,Torzewski J.C-reactive protein mediated low density lipoprotein uptakebymacrophages:implications for atherosclerosis.Circulation,2001,103:1194-1197.
20.Jernkins A J,Best JD,Klein RL,et al.Lipoproteins,glycoxidation and diabetic angiopathy.Diabetes Metab Res Rev.2004;20:349-368.
21.Saely CH,Koch L,Schmid F,et al.Lipoprotein(a),type 2 diabetes and vascular risk in coronary patients.Eur J Clin Invest.2006,36:91-97.
22.Retterstol L,Eikvar L,Bohn M,et al.C-reactive protein predicts death in patients with previous premature myocardial infarction-a 10 year follow up study[J].Therosclerosis,2002,160:433-440.
1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s [J]. Nature 1993 Apr 29; 362 (6423): 801-09.
2. Ross R, Glomset JA. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis [J].Science 1973; 180(93): 1332-339.
3. Blaschke F, Leppanen O, Takata Y, et al. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries [J]. Cir Res. 2004; 95(12):e110-23.
4. David WM, Muller. The role of proto-oncogene in coronary restenosis [J]. Prog in Cardiovasc Dis. 1997,40:117-128.
5. Katakami N, Kaneto H, Hao H, et al. Role of pim-1 in smooth muscle cell proliferation [J]. J Biol Chem. 2004,279(52):5472-9.
6. Wang CH, Verma S, Hsieh IC, et al. Stem cell factor attenuates vascular smooth muscle apoptosis and increases intimal hyperplasia after vascular injury [J]. Arterioscler Thromb Vasc Biol. 2007, 27(3):540-7.
7. Zhang YR, Zhang YX, Cao W, et al. Uptake kinetics of 99mTc-MAG3-antisense oligonucleotide to PCNA and effect on gene expression in vascular smooth muscle cells [J]. J Nucl Med. 2005,46(6):1052-8.
8. Opitz F, Schenke-Layland K, Richter W, et al. Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells [J]. Ann Biomed Eng. 2004, 32(2):212-22.
9. Shebing Zhang, Junshi Liu, Jinsheng Li. Molecular biology mechanism of endomembrane proliferation after angioplasty [J]. Journal of Xiangnan University (Natural Sciences). 2004, 6(3):64-68.
10. Jie Chen, Hongyi Wang, Jin Tao, Huae Xu, Rong Yang, Shengnan Li. Urocortin, the neuropeptide, inhibits the viability of ECV304 cells and rat vascular smooth muscle cells [J]. Journal of Nanjing Medical University 2004,18(1) 1-3.
11. Aihua Zhang, Songming Huang, Guixia Ding, Yuanjun Wu, Weizhen Zhang, Hongmei Wu, Li Fei, Mei Guo, Ronghua Chen. JNK-c-Jun/AP-1 Signal Pathway Regulated Angiotensin II-induced Human Mesangial Cells Proliferation [J]. Journal of Nanjing Medical University 2004, 24 (1) 4-8.
12. Wang XQ, Su X, Liu HM, et al. Effect of truncated PDGF-alpha receptor on proliferation and expression of c-sis mRNA of vascular smooth muscular cells of pulmonary artery [J]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005,36(6):804-7.
13. Lincoln TM, Wu X, Sellak H, et al. Regulation of vascular smooth muscle cell phenotype by cyclic GMP and cyclic GMP-dependent protein kinase [J]. Front Biosci.2006,11:356-67.
14. Kim TJ, Yun YP. Potent inhibition of serum-stimulated responses in vascular smooth muscle cell proliferation by 2-chloro-3-(4-hexylphenyl)-amino-l, 4-naphthoquinone, a newly synthesized 1, 4-naphthoquinone derivative [J]. Biol Pharm Bull. 2007,30(1):121-7.
15. Green CM. One ring to rule them all? Another cellular responsibility for PCNA [J].Trends Mol Med. 2006,12(10):455-8.
16. Biro S, Fu YM, Yu ZX, et al. Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration [J]. Proc Natl Acad Sci USA, 1993; 90(2):654~8.
17. Jiefang Bian, Baigen Zhang, Shishu Chen, et al. Gene segment of antisense PCNA depress the expression of gene correlated with VSMC [J]. Chinese Medical Journal,1999, 79(1):10-14.
18. Puqing Zeng, Tongguang Wang, Zhaohui Zhu, et al. Study on the proliferation of carcinoma cell of bladder BIU-87PCNA depressed by antisense oliganucleotides in vitro [J]. Chinese Journal of Urology, 1999:20(4):231-233.
19. De Nigris F, Sica V, Herrmann J, et al. c-Myc pncoprotein: cell cycle-related events and new therapeutic challenges in cancer and cardiovascular diseases [J]. Cell Cycle. 2003,2(4):325-8.
20. Jingyi Su. Cardiovascular disease pathology physiology foundation and pathogenesis.Beijing: Beijing medical college, Chinese Harmony Medical college unites the publishing house, 1994, 359.
21. HB Li, F Chen. Preparative isolation and purification of chuanxiongzine from the medicinal plant ligusticum chuanxiong by high-speed counter-current chromatograph. J Chromatogr A2004,1047: 249-53.
22. Badimen JJ, Fuster V, chessebro JH, Badimon L. Coronary atherosclerosis: a muitifactorial disease. Circulation 1993.87:3-16.
23. Nassar BA, Rockwood K, Kirkland SA, Ransom TP, Darvesh S, MacPherson K,Johnstone DE, O'Neill BJ, Bata IR, Andreou P, Jeffery JS, Cox JL, Title LM. Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K,PPARgamma2 Prol2 and ENOS T-786C in a polygenic model. Clin Biochem 2006;39(2): 109-14.
24. Qingguo Tao, Zhenxiang Zhang, Yongjian Xu. Research on the cell multiplication and apotosis in the chronicity blocking pulmonic disease. Chinese medical journal. 1998, 78:574-577.
25. Jie Chen, Hongyi Wang, Jin Tao, Huae Xu, Rong Yang, Shengnan Li. Urocortin, the neuropeptide, inhibits the viability of ECV304 cells and rat vascular smooth muscle cells. Journal of Nanjing Medical University 2004,18(1) 1-3.
26. Sanmei Zhao, Renyi Xia, Zongli Wang, Mingpeng Yu. Artery smooth muscle cell raise method and function. Chinese Journal of Pathology 1987; 16 (4): 260-61.
27. Jane AM, Daniel ER, Peter A K, Jack GK. Ion exchange activity in pulmonary artery smooth muscle cells: the response to hypoxia. Am J Physiol Lung Cell Mol Physiol 2001, 280: L264-L71.
28. Ziqing Gao, Qinghuai Liu, Ping Xie, Xiaoyi Liu. Influence of transforming growth factor β_1(TGF-β_1) on human orbital fibroblasts proliferation. Journal of Nanjing Medical University 2005 25(5): 294-296,300.
29. Malcolm C, William EA, Carol S, et al. Glucose-Potentiated Chemotaxis in Human Vascular Smooth Muscle Is Dependent on Cross-Talk Between the PI3K and MAPK Signaling Pathways. Cir. Res. 2004, 95(4): 380-88.
30. Hongwei Wang, Lu Zhang, Huayue Zhao. Effects of Tetramethylpyrazine on c-myc Gene Expression in Vascular Smooth Muscle Cells and Proliferation of Vascular Smooth Muscle Cells. Chinese journal of arteriosclerosis 2000, 8(4): 319-21.
31. Xianjie Yu, Jinxiang Wu, Xinxing Wang. The inhibitory action and the mechanism of chuanxiongzine on the multiplication of VSMC. Journal of Social Science of Hunan Medical University 1992,17(4): 350-53.
32. Jing Leng, Yuyu Yao, Hang Yin, Jun Huang, Tao Peng. Studies on the Apoptotic Inducement Effects of Fluorouracil and Lisinopri 1, and c-myc, c-fos, p53 Gene Expressions on Cultured Synthetic Smooth Muscles. Journal of Nanjing Medical University 2001,19 (5):382-84.
33. Morisaki N, Kanonom, Koyama N, Koshikawa T, Umemiya K, Saito Y, Yoshida S.Effects of transformig growth factor-β_1 on growth of aortic smooth muscle cells.Atherosclerosis 1991, 88:227-34.
34. Yamamoto M, Yamamoto K. Growth regulation in primary culture of rabbit arterial smooth muscle cells by platelet-derived growth factor, insulin-like growth factor-1, and epidermal growth factor. Exp Cell Res 1994,212:62-68.
35. Weixing Gong. Chuanxiongzine cardiovascular pharmacology research progress.Chinese Journal of Hospital Pharmacy 1990,10(11): 511-13.
36. Yazhuo Zhang, Xiaoguang Chen, Qingcheng Xue. Reperfusion injury effect of Danggui and chuanxiongzine on cerebral anoxia and ischemia. Journal of Jia Mu si Medical college 1990,13(3): 210-13.
1. Galis ZS, Johnson C, Godin D, et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial rremodeling. Circ res, 2002,91:852-859.
2. Fuster v Fallon JT, Nemerson Y. Coronary thrombsis. Lancet, 1996,348(1):7-10.
3. O'Brien ER, Garvin MR, Dev R, et al. Angiogenesis in human coronary atherosclerotic plaques. Am J Pathol, 1994,145:883-894.
4. Depre C, Havaux X, Wijns W. Neovascularization in human coronary atherosclerotic lesions. Cather Cardiovasc Diagn, 1996,39:215-220.
5. Bueke AP, Virmani R, Galis Z, et al. 34~(th) Bethesda Conference:Task force ~#2-What is the pathologic basis for new atherosclerosis imaging techniques? J Am Coll Cardiol,2003,41:1874-1886.
6. Nasu K, Tsuchikane E, and Katoh O, et al. Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopahthology. J Am Coll Cardiol, 2006,47(12):2405-2412.
7. Jensen LO, Mintz GS, Carlier SG, et al. Intravascular ultrasound assessment of filbrous cap remnants afer coronary plaque rupture. Am Heart J, 2006,152(2):327-332.
8. Nakamura R, Ito K, Koide M, et al. Coronary artery plaque assessment using Volcano Therapeutics' Virtual Histology intravascular ultrasound and temperature guide wire. J Cardiol, 2006,48(2):85-92.
9. Yamagishi M, Terashima M, Awano K, et al. Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. J Am Coll Cardiol, 2000, 35(1):106-111.
10. Nair A, Kuban BD, Obuchowski N, et al. Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data. Ultrasound Med Biol, 2001, 27(10):1319-1331.
11. Kawasaki M, Bouma BE, Bressner J, et al. Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques. J Am Coll Cardiol, 2006, 48(1):81-88.
12. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part Ⅰ: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001; 104:2746-2753.
13. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J,Weiss M, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988; 12:56-62.
14. Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kah1 FR,Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157-1166.
15. Brensike JF, Levy RI, Kelsey SF, Passamani ER, Richardson JM, Loh IK, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation 1984; 69:313-324.
16. de Servi S, Mazzone A, Ricevuti G, Mazzucchelli I, Fossati G, Angoli L, et al.Expression of neutrophil and monocyte CD11B/CD18 adhesion molecules at different sites of the coronary tree in unstable angina pectoris. Am J Cardiol 1996; 78:564-568.
17. Falk E. Plaque ruptures with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983; 50:127-134.
18. Davies MJ, Thomas AC. Plaque fissuring - the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985; 53:363—373.
19. Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, Virmani R. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93:1354-1363.
20. Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, et al.Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 2003;349:2316-2325.
21. Muller JE, Abela GS, Nesto RW, Tofler GH. Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier. J Am Coll Cardiol 1994; 23:809-813.
22. Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 2001; 16: 285-292.
23. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69:377-381.
24. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 1994; 90:775-778.
25. Loree HM, Kamm RD, Stringfellow RG, Lee RT. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res 1992;71:850-858.
26. Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; ii: 941-944.
27. Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844-2850.
28. Lee RT, Schoen FJ, Loree HM, Lark MW, Libby P. Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis. Implications for plaque rupture.Arterioscler Thromb Vasc Biol 1996; 16:1070-1073.
29. Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77:863-868.
30. Galis ZS, Sukhova GK, Lark MW, libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94:2493-2503.
31. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation 2003; 108:1664-1672.
32. Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, et al.Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol 1991; 18:904-910.
33. Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography.Am J Cardiol 1992; 69:729-732.
34. Di Mario C, The SH, Madretsma S, van Suylen RJ, Wilson RA, Bom N, et al.Detection and characterization of vascular lesions by intravascular ultrasound: an in vitro study correlated with histology. J Am Soc Echocardiogr 1992; 5:135-146.
35. Potkin BN, Bartorelli AL, Gessert JM, Neville RF, Almagor Y, Roberts WC, et al.Coronary artery imaging with intravascular high-frequency ultrasound. Circulation 1990; 81:1575-1585.
36. Rasheed Q, Dhawale PJ, Anderson J, Hodgson JM. Intracoronary ultrasound-defined plaque composition: computer-aided plaque characterization and correlation with histologic samples obtained during directional coronary atherectomy. Am Heart J 1995;129:631-637.
37. Hiro T, Leung CY, Russo RJ, Karimi H, Farvid AR, Tobis JM. Variability of a three-layered appearance in intravascular ultrasound coronary images: a comparison of morphometric measurements with four intravascular ultrasound systems. Am J Card Imaging 1996; 10:219-227.
38. Yamagishi M, Terashima M, Awano K, Kijima M, Nakatani S, Daikoku S, et al.Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. J Am Coll Cardiol 2000;35:106-111.
39. Nakamura M, Nishikawa H, Mukai S, Setsuda M, Nakajima K, Tamada H, et al.Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol 2001; 37:63-69.
40. Maehara A, Mintz GS, Bui AB, Walter OR, Castagna MT, Canos D, et al. Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound. J Am Coll Cardiol 2002; 40:904- 910.
41. Kotani J, Mintz GS, Castagna MT, Pinnow E, Berzingi CO, Bui AB, et al.Intravascular ultrasound analysis of infarct-related and non-infarct-related arteries in patients who presented with an acute myocardial infarction. Circulation 2003;107:2889-2893.
42. Carlier S, Kakadiaris IA, Dib N, Vavuranakis M, O'Malley SM, Gul K, et al. Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep 2005; 7:164-169.
43. Jeremias A, Kolz ML, Ikonen TS, Gummert JF, Oshima A, Hayase M, et al. Feasibility of in vivo intravascular ultrasound tissue characterization in the detection of early vascular transplant rejection. Circulation 1999; 100:2127-2130.
44. Fujimoto JG, Bouma B, TearneyGJ, Boppart SA, Pitris C, Southern JF, et al. New technology for high-speed and high-resolution optical coherence tomography. Ann NY Acad Sci 1998; 838:95-107.
45. Brezinski ME, Tearney GJ, Bouma B, Boppart SA, Hee MR, Swanson EA, et al.Imaging of coronary artery microstructure (in vitro) with optical coherence tomography.Am J Cardiol 1996; 77:92-93.
46. Patwari P, Weissman NJ, Boppart SA, Jesser C, Stamper D, Fujimoto JG, Brezinski ME. Assessment of coronary plaque with optical coherence tomography and high-frequency ultrasound. Am J Cardiol 2000; 85:641- 644.
47. Yabushita H, Bouma BE, Houser SL, Aretz HT, Jang IK, Schlendorf KH, et al.Characterization of human atherosclerosis by optical coherence tomography.Circulation 2002; 106:1640-1645.
48. Brezinski ME, Tearney GJ, Weissman NJ, Boppart SA, Bouma BE, Hee MR, et al.Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound. Heart 1997; 77:397-403.
49. Regar E, Schaar JA, van der Giessen W, van der Steen AF, Serruys PW. Real-time,in-vivo optical coherence tomography of human coronary arteries using a dedicated imaging wire. Am J Cardiol 2002; 90: 129H,
50. Tearney GJ, Yabushita H, Houser SL, Aretz HT, Jang IK, Schlendorf KH, et al.Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 2003; 107:113-119.
51. Peters RJ, Kok WE, Bot H, Visser CA. Characterization of plaque components with intracoronary ultrasound imaging: an in vitro quantitative study with videodensitometry. J Am Soc Echocardiogr 1994; 7:616-623.
52. Schmermund A, Erbel R. Unstable coronary plaque and its relation to coronary calcium. Circulation 2001; 104:1682-1687.
53. Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis.Circulation 2002; 106:2200-2206.
54. Nair A, Kuban BD, Obuchowski N, Vince DG. Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data. Ultrasound Med Biol 2001; 27:1319-1331.
55. Virmani R, Burke AP, Farb A. Sudden cardiac death. Cardiovasc Pathol 2001;10:211-218.
56. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 1999;138:S421-S425.
57. Burleigh MC, Briggs AD, Lendon CL, Davies MJ, Born GV, Richardson PD. Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations. Atherosclerosis 1992; 96:71-81.
58. Lendon CL, Davies MJ, Richardson PD, Born GV. Testing of small connective tissue specimens for the determination of the mechanical behaviour of atherosclerotic plaques.J Biomed Eng 1993; 15:27-33.
59. Cespedes EI, de Korte CL, van der Steen AF, von Birgelen C, Lancee CT.Intravascular elastography: principles and potentials. Semin Interv Cardiol 1997;2:55-62.
60. de Korte CL, Pasterkamp G, van der Steen AF, Woutman HA, Bom N.Characterization of plaque components with intravascular ultrasound elastography in human femoral and coronary arteries in vitro. Circulation 2000; 102:617-623.
61. Schaar JA, De Korte CL, Mastik F, Strijder C, Pasterkamp G, Boersma E, et al.Characterizing vulnerable plaque features with intravascular elastography. Circulation 2003; 108:2636-2641.
62. de Korte CL, SierevogelMJ, Mastik F, Strijder C, Schaar JA, Velema E, et al.Identification of atherosclerotic plaque components with intravascular ultrasound elastography in vivo: a Yucatan pig study. Circulation 2002; 105:1627-1630.
63. de Korte CL, Carlier SG, Mastik F, Doyley MM, van der Steen AF, Serruys PW, Bom N. Morphological and mechanical information of coronary arteries obtained with intravascular elastography; feasibility study in vivo. Eur Heart J 2002; 23:405-413.
64. Doyley MM, Mastik F, de Korte CL, Carlier SG, Cespedes EI, Serruys PW, et al.Advancing intravascular ultrasonic palpation toward clinical applications. Ultrasound Med Biol 2001; 27:1471-1480.
65. Schaar JA, Regar E, Mastik F, McFadden EP, Saia F, Disco C, et al. Incidence of high-strain patterns in human coronary arteries: assessment with three-dimensional intravascular palpography and correlation with clinical presentation. Circulation 2004;109:2716-2719.
66. Fuster V. Human lesion studies. Ann NY Acad Sci 1997; 811:207-224.
67. Stefanadis C, Diamantopoulos L, Vlachopoulos C, Tsiamis E, Dernellis J, Toutouzas K,et al. Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: a new method of detection by application of a special thermography catheter.Circulation 1999; 99:1965-1971.
68. Stefanadis C, Toutouzas K, Tsiamis E, Stratos C, Vavuranakis M, Kallikazaros I, et al.Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention. J Am Coll Cardiol 2001; 37:1277-1283.
69. Stefanadis C, Toutouzas K, Tsiamis E, Mitropoulos I, Tsioufis C, Kallikazaros I, et al.Thermal heterogeneity in stable human coronary atherosclerotic plaques is underestimated in vivo: the 'cooling effect' of blood flow. J Am Coll Cardiol 2003;41:403-408.
70. Have AG, Gijsen FJ, Wentzel JJ, Slager CJ, van der Steen AF. Temperature distribution in atherosclerotic coronary arteries: influence of plaque geometry and flow (a numerical study). Phys Med Biol 2004; 49:4447-4462.
71. Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Arai T, et al.Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med 1992; 326:287-291.
72. Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, Chaux A, et al. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 1986;315:913-919.
73. Mizuno K, Miyamoto A, Satomura K, Kurita A, Arai T, Sakurada M, et al.Angioscopic coronary macromorphology in patients with acute coronary disorders.Lancet 1991; 337:809-812.
74. Feld S, Ganim M, Carell ES, Kjellgren O, Kirkeeide RL, Vaughn WK, et al.Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients. J Am Coll Cardiol 1996; 28:97-105.
75. Takano M, Mizuno K, Okamatsu K, Yokoyama S, Ohba T, Sakai S. Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound. J Am Coll Cardiol 2001; 38:99-104.
76. Ueda Y, Ohtani T, Shimizu M, Hirayama A, Kodama K. Assessment of plaque vulnerability by angioscopic classification of plaque color. Am Heart J 2004;148:333-335.
77. Baraga JJ, Feld MS, Rava RP. In situ optical histochemistry of human artery using near infrared Fourier transforms Raman spectroscopy. Proc Natl Acad Sci USA 1992;89:3473-3477.
78. Wang J, Geng YJ,Guo B, Klima T, Lal BN, Willerson JT, Casscells W. Nearinfrared spectroscopic characterization of human advanced atherosclerotic plaques. J Am Coll Cardiol 2002; 39:1305-1313.
79. Moreno PR, Muller JE. Identification of high-risk atherosclerotic plaques: a survey of spectroscopic methods. Curr Opin Cardiol 2002; 17:638-647.