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Relationship between tissue type plasminogen activator and coronary vulnerable plaque in patients with acute coronary syndrome： virtual histological study

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Chinese Medical Journal 2008年第6期121卷 540-543页

作者： WANG Hai-bin KANG Wei-qiang SONG Da-lin WANG Xu REN Guo-rui TENG Jin-long GE Zhi-ming Medical College of Shandong University Jinan Shandong 250012China Department of Cardiology Qingdao Municipal Hospital QingdaoShandong 266001 China Department of Cardiology Affiliated Hospital of Medical College ofQingdao University Qingdao Shandong 266001 China Department of Cardiology Qilu Hospital Shandong UniversityJinan Shandong 250012 China

Background The association between vulnerability of plaque assessed with intravascular ultrasound （IVUS） and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome （ACS）. However, few data are available on the relationship between the levels of tissue type plasminogen activator （t-PA） and virtual histological intravascular ultrasound （VH-IVUS） signs of plaque instability. Methods Eighty-nine patients with ACS were enrolled in the study. Blood was collected to measure t-PA levels by liquid phase bead flow cytometry. Eighty-nine nonbifurcate lesions （identified by coronary angiography and ECG） were investigated using IVUS before catheterization. IVUS radiofrequency data obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software. The areas of plaque and media were calculated and lesions were classified into two groups： VH-IVUS derived thin cap fibroatheroma （VH-TCFA） and non-VH-TCFA plaque. Results Plasma t-PA level in the patients with TCFA was significantly lower than that with non-TCFA （（1489 ± 715） pg/ml vs （2163 ± 1004） pg/ml）. Decreased plasma levels of t-PA were associated with plaque vulnerability. Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS. Conclusions t-PA is an independent risk factor and a powerful predictor of vulnerable plaques. Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.

关键词： acute coronary syndrome tissue type plasminogen activator vulnerable plaque diagnostic technique intravascular ultrasound

Local aneurysmal dilatation mimicking stent malapposition and concurrent vulnerable plaque within neointima of normal lumen after drug-eluting stent implantation： primary new findings from optical coherence tomography

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Chinese Medical Journal 2012年第6期125卷 1186-1188页

作者： GUO Yuan-lin YANG Yue-jin GAO Zhan QIAN Jie Clinical and Research Center for Coronary Disease Fu Wai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Very late stent thrombosis is a life-threatening complication of implantation of drug-eluting stent （DES）. The mechanisms are still unidentified. Stent malapposition is supposed to be one debated reason. Here we report a case of 33 months after DES implanted. Observed by optical coherence tomography, we detected a lipid-rich plaque with defective fibrous cap within the neointima and many local aneurysmal dilatations between stent struts, which mimic ＂malapposition＂ on the angiogram. These indicated that vulnerable plaque hidden in the neointima at the stent segment might be a potential mechanism of very late stent thrombosis after DES implantation.

关键词： drug-eluting stent stent malapposition vulnerable plaque optical coherence tomography

Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

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Chinese Medical Journal 2011年第6期124卷 911-917页

作者： ZHAO Quan-ming FENG Ting-ting ZHAO Xin XU Zhan-min LIU Yu LI De-peng LI Li-qin SU Gong ZHANG Xiao-xia Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing 100029 China Institute of Basic Medicine Capital Medical University Beijing 100069 China Center for PET/CT General Hospital of Second Artillery of People's Liberation Army Beijing 100088 China

Abstract：Background Atherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture （vulnerable plaque） could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose （18F-FDG）. The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit *** Ten male New Zealand White rabbits were divided into three groups as follows：（1） normal control group （n=2,C group）： the animals were fed a standard diet at 120 g/d and were given water ad labium; （2） atherosclerosis group （n=4,As group）： animals were fed with high fat diet for 5 months after aortic endothelia damage; （3） treatment group （atherosclerosis ＋ atorvastatin, n=4, Statin group）： animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin （2.5 mg·d-1·kg-1） treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodexyglucose positron emission tomography/computed tomography （PET/CT） and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio （TBR）. Maximal standardized uptake value （SUV） was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell （SMC） number, CD-14 antibody positive cell （macrophage） number and the ratio of the thickness of fibrous cap to the thickness of lipid core （cap-to-core ratio） in atherosclerotic plaques were *** As group showed significantly higher uptake of FDG than C group （SUVs： 0.746±0.172 vs. 0.286±0.073, P 〈0.001）. After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly （Statin group：0.550±0.134, compared to As grou

关键词： fluorine-18 fluorodeoxyglucose positron emission tomography angiography vulnerable plaque inflammation

Relationship between plasma cathepsin S and cystatin C levels and coronary plaque morphology of mild to moderate lesions： an in vivo study using intravascular ultrasound

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Chinese Medical Journal 2009年第23期122卷 2820-2826页

作者： GU Fei-fei LV Shu-zheng CHEN Yun-dai ZHOU Yu-jie SONG Xian-tao JIN Ze-ning LIU Hong Department of Cardiology Beijing Anzhen Hospital CapitalMedical University Beijing 100029 China Heart Center China Meitan General Hospital Beijing 100028China Department of Cardiology Chinese People's Liberation ArmyGeneral Hospital Beijing 100853 Cbina

Background Cathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis, especially in the plaque destabilization and rupture leading to acute coronary syndrome. However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet. Methods We recruited 98 patients with unstable angina （UA, n=56） or stable angina （SA, n=-42） who had a segmental stenosis resulting in 〉20% and 〈70% diameter reduction in one major coronary artery on coronary angiography. Thirty-one healthy subjects served as controls. Intravascular ultrasound （IVUS） was used to evaluate plaque morphology. Plasma cathepsin S and cystatin C were measured as well. Results At the culprit lesion site, plaque area （（7.85±2.83） mm^2 vs （6.53±2.92） mm^2, P=0.027）, plaque burden （（60.92±11.04）% vs （53.87±17.52）%, P=0.025）, remodeling index （0.93±0.16 vs 0.86±0.10, P=0.004） and eccentricity index （0.74±0.17 vs 0.66±0.21, P=0.038） were bigger in UA group than in SA group. Plasma cathepsin S and cystatin C were significantly higher in patients than in controls （P〈0.01）. Plasma cathepsin S was higher in UA group （（0.411±0.121） nmol/L） than in SA group （（0.355±0.099） nmol/L, P=0.007）, so did the plasma cystatin C （（0.95±0.23） mg/L in UA group, （0.84±0.22） mg/L in SA group; P=0.009）. Plasma cathepsin S positively correlated with remodeling index （r=0.402, P=0.002） and eccentricity index （r=0.441, P=0.001）, and plasma cystatin C positively correlated with plaque area （r=0.467, P 〈0.001） and plaque burden （r=0.395, P=0.003） in UA group but not in SA group. Conclusions Plasma cathepsin S and cystatin C increased significantly in UA patients. In angina patients, higher plasma cathepsin S may suggest the presence of vulnerable plaque, and higher plasma cystatin C may be a clue for larger atherosclerotic coronary plaque.

关键词： cathepsin S cystatin C, intravascular ultrasound atherosclerosis vulnerable plaque

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation

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Chinese Medical Journal 2012年第24期125卷 4380-4385页

作者： CHEN Li CHENG Wen-li WANG Yong KE Yuan-nan FAN Shu-ying PAN Lin GUO Yan-ru LI Hong GUO Jian Department of National Integrative Medicine Center for Cardiovascular Disease China-Japan Friendship Hospital Beijing 100029 China Clinical Medical Research Institute China-Japan Friendship Hospital Beijing 100029 China

Background vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation （ALMP） on vulnerable plaques in the brachiocephalic artery of apolipoprotein E （Apo E） knockout mice. Methods Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose （3.6 μg, kg-1. d-1） or low dose （1.8 μg. kg-1 . d-1） of an ALMP, or 0.2 ml/d normal saline （control group）, The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody （MOMA-2） and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 （ICAM-1） expression was measured by ELISA, and the expression of matrix metalloproteinase-9 （MMP-9） and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 （TSP-1） expression was detected using Western blotting. Results Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery （P 〈0.01）, significantly lowered the contents of the lipid core （P 〈0.01 ）, significantly reduced the number of ruptured fibrous caps （P 〈0.05）, and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage （P 〈0.05）. ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques （P 〈0.01）, decreased plasma ICAM-1 expression （P 〈0.01 ）, and increased the expression of TSP-1. Conclusions Treatment with ALMP can stab

关键词： vulnerable plaque atherosclerosis alprostadil liposome microsphere preparation

Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis

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Heme oxygenase-1 inhibits progression and destabilization of...

Evaluation of Carotid plaque Neovascularization in Patients with Diabetes Mellitus by Contrast-enhanced Ultrasonography

山东省医学会第十一次老年医学分会学术会

作者： Li Tingting Tian Hongbo Zhao Yuxia An Fengshuang Zhang Lei Zhang Jianning Peng Jie Zhang Yun Guo Yuan The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of HealthShandong University Qilu Hospital Department of Cardiology Provincial Hospital affiliated to Shandong University

＜正＞Although heme oxygenase-1（HO-1） has been implicated in protection against atherogenesis,its role in vulnerable plaques remains to be fully *** study was aimed to explore the effect of HO-1 on the progression and stabilization of vulnerable plaques and the possible *** established a vulnerable plaque model by local transfection with recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet HO-1 activity was modulated by intraperitoneal injection of hemin or Sn-protoporphyrinⅨ（SnPP）.HO-1 induction by hemin inhibited the progression of atherosclerotic lesions and changed the plaque morphology and composition into a more stable *** addition,hemin treatment is associated with a reduction in matrix metalloproteinase-9,interleukin-6 and tumor necrosis factor-αproduction,an increase in interleukin-10 level,as well as a decrease of TUNEL labeled apoptosis of smooth muscle cells in *** with the control group,aortic nitric oxide（NO） production and inducible nitric oxide synthase（iNOS） activity decreased markedly,whereas endothelial nitric oxide synthase（eNOS） activity increased significantly in the Hemin *** contrast,inhibition of HO-1 by SnPP induced reversed effects and augmented plaque progression and *** pharmacological triggering,the incidence of plaque disruption in SnPP group was significantly higher than that in control group（79%vs.33%,P＜0.05）,while no plaque in Hemin group developed disruption（0%vs.33%,P＜0.05）.These findings suggest that HO-1 induction could delay progression and enhance stability of atherosclerotic plaques,possibly through the attenuation of plaque inflammation and apoptosis,and the suppression of iNOS/NO production.

关键词： vulnerable plaque Inflammation Apoptosis Nitric oxide Heme oxygenase

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第1期34卷 29-32页

作者：熊莉黎鹏赵博文 Department of Medical Ultrasound Sir Run Run Shaw Hospital Zhejiang University

This study investigated the relationship between carotid plaque neovascularization and diabetes mellitus（DM） by using contrast-enhanced ultrasonography. Contrast-enhanced ultrasonography was performed in 104 patients with carotid plaque thicker than 2.0 mm. There were 36 patients with DM and 68 patients without DM. The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery in patients with DM were significantly greater than those in patients without DM. Our study demonstrated that the enhanced intensity in patients with DM is greater than that their counterparts without DM, suggesting that carotid plaque in DM patients may have more neovessels and may be more vulnerable.

关键词： vulnerable plaque contrast-enhanced ultrasonography diabetes mellitus neovasculari-zation

Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

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Frontiers of Medicine 2010年第1期4卷 36-42页

作者： Wen-Qiang CHEN Yun ZHANG The Key Laboratory of Cardiovascular Remodeling and Function Research Ministry of Education and Ministry of HealthShandong University Qilu HospitalJinan 250012China

vulnerable atherosclerotic plaque rupture lead-ing to thrombosis is the major cause of acute coronary syndrome(ACS).Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable *** our laboratory,we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque *** mechanisms involved in plaque vulnerability were studied from the inﬂammation-immunity,proliferation-apoptosis,oxidative stress and biomechanics *** markers and biomarkers were used to detect vulnerable plaques,including high frequency duplex ultrasound,intravascular ultrasound(IVUS),intravascular ultrasound elastography,magnetic resonance imaging(MRI)and inﬂammatory *** gene and drug strategies to treat vulnerable plaques were explored.

关键词： vulnerable plaque animal models mechani-sm detection treatment

The possible value of ~18F-FDG positron emission tomography/computerized tomography imaging in detection of atherosclerotic plaque

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Journal of Nanjing Medical University 2008年第1期22卷 61-65页

作者： Jianwei Yuan Yanlin Feng Lingxiao Fan Xiaohong He Departrnent of Nuclear Medicine Affiliated Foshan Hospital of Sun Yat-sen University Foshan 528000 Guangdong Province China Office of Scientific Research Management zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080

Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.

关键词： fluorine-18-2-fluoro-2-deoxy-D-glucose positron-emission tomography computerized, tomography atherosclerosis vulnerable plaque