Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2010, Vol. 4 Issue (1) : 36-42     DOI: 10.1007/s11684-010-0020-y
Research articles |
Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques
Wen-Qiang CHEN MD,Yun ZHANG MD, PhD, FACC,
The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Health, Shandong University Qilu Hospital, Jinan 250012, China;
Download: PDF(107 KB)  
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract  Vulnerable atherosclerotic plaque rupture leading 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 plaque. In our laboratory, we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture. Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity, proliferation-apoptosis, oxidative stress and biomechanics aspects. Imaging 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 markers. Effective gene and drug strategies to treat vulnerable plaques were explored.
Keywords vulnerable plaque      animal models      mechani-sm      detection      treatment      
Issue Date: 05 March 2010
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-010-0020-y     OR     http://academic.hep.com.cn/fmd/EN/Y2010/V4/I1/36
Ni M, Chen W Q, Zhang Y. Animal models and potential mechanismsof plaque destabilization and disruption. Heart, 2009, 95(17): 1393–1398

doi: 10.1136/hrt.2008.143461
Chen W Q, Zhang Y, Zhang M, Yin Y, Zhu Y F. Establishing an animal modelof unstable atherosclerotic plaques. ChinMed J (Engl), 2004, 117(9): 1293–1298
Chen W Q, Zhang L, Liu Y F, Chen L, Ji X P, Zhang M, Zhao Y X, Yao G H, Zhang C, Wang X L, Zhang Y. Prediction of atherosclerotic plaque ruptures with high-frequencyultrasound imaging and serum inflammatory markers. Am J Physiol Heart Circ Physiol, 2007, 293(5): H2836–H2844

doi: 10.1152/ajpheart.00472.2007
Lin H L, Xu X S, Lu H X, Zhang L, Li C J, Tang M X, Sun H W, Liu Y, Zhang Y. Pathologicalmechanisms and dose dependency of erythrocyte-induced vulnerabilityof atherosclerotic plaques. J Mol Cel Cardiol, 2007, 43(3): 272–280

doi: 10.1016/j.yjmcc.2007.05.023
Ni M, Wang Y, Zhang M, Zhang P F, Ding S F, Liu C X, Liu X L, Zhao Y X, Zhang Y. Atheroscleroticplaque disruption induced by stress and lipopolysaccharide in apolipoproteinE knockout mice. Am J Physiol Heart CircPhysiol, 2009, 296(5): H1598–1606

doi: 10.1152/ajpheart.01202.2008
Ni M, Zhang M, Ding S F, Chen W Q, Zhang Y. Micro-ultrasound imagingassessment of carotid plaque characteristics in apolipoprotein-Eknockout mice. Atherosclerosis, 2008, 197(1): 64–71

doi: 10.1016/j.atherosclerosis.2007.07.039
Zhang M X, Zhang C, Shen Y H, Wang J, Li X N, Zhang Y, Coselli J, Wang X L. Biogenesis of short intronicrepeat 27 nt small RNA from endothelial nitric oxide synthase gene. J Biol Chem, 2008, 283(21): 14685–14693

doi: 10.1074/jbc.M801933200
Zhang M X, Zhang C, Shen Y H, Wang J, Li X N, Chen L, Zhang Y, Coselli J S, Wang X L. Effect of 27nt small RNA on endothelial nitric oxidesynthase expression. Mol Biol Cell, 2008, 19(9): 3997–4005

doi: 10.1091/mbc.E07-11-1186
Zhong L, Chen W Q, Ji X P, Zhang M, Zhao Y X, Yao G H, Zhang P F, Zhang C, Zhang Y. Dominant-negativemutation of monocyte chemoattractant protein-1 prevents vulnerableplaques from rupture in rabbits independent of serum lipid levels. J Cell Mol Med, 2008, 12(6A): 2362–2371

doi: 10.1111/j.1582-4934.2008.00261.x
Zhang C, Zhang M X, Shen Y H, Burks J K, Zhang Y, Wang J, LeMaire S A, Yoshimura K, Aoki H, Coselli J S, Wang X L. TNF-alpha suppresses prolyl-4-hydroxylasealpha1 expression via the ASK1-JNK-NonO pathway. Arterioscler Thromb Vasc Biol, 2007, 27(8): 1760–1767

doi: 10.1161/ATVBAHA.107.144881
Zhang C, Zhang M, Shen Y, Burks J, Li X, LeMaire S, Yoshimura K, Aoki H, Matsuzaki M, An F, Engler D, Matsunami R, Coselli J, Zhang Y, Wang X. Role of NonO-histoneinteraction in TNFα-suppressed prolyl-4-hydroxylase α1. Biochim Biophys Acta, 2008, 1783(8): 1517–1528

doi: 10.1016/j.bbamcr.2008.03.011
Guo T, Chen W Q, Zhang C, Zhao Y X, Zhang Y. Chymase activity is closelyrelated with plaque vulnerability in a hamster model of atherosclerosis. Atherosclerosis, 2009, 207(1): 59–67

doi: 10.1016/j.atherosclerosis.2009.04.014
Dong B, Zhang C, Feng J, Zhao Y, Li S, Yang Y, Dong Q, Deng B, Zhu L, Yu Q, Liu C, Liu B, Pan C, Song H, Zhang M, Zhang Y. Overexpression of ACE2 enhances plaque stability in arabbit model of atherosclerosis. ArteriosclerThromb Vasc Biol, 2008, 28(7): 1270–1276

doi: 10.1161/ATVBAHA.108.164715
Liu P, Zhang C, Feng J B, Zhao Y X, Wang X P, Yang J M, Zhang M X, Wang X L, Zhang Y. Cross-talkamong smad, MAPK, and integrin signaling pathways enhances adventitialfibroblast functions activated by transforming growth factor {beta}1 and inhibited by Gax. Arterioscler ThrombVasc Biol, 2008, 28(4): 725–731

doi: 10.1161/ATVBAHA.107.159889
Xu X S, Lin H L, Lv H X, Zhang M, Zhang Y. Adventitial lymphatic vessels,an important role in atherosclerosis. MedHypotheses, 2007, 70(1): 1238–1241

doi: 10.1016/j.mehy.2007.04.007
Xu X, Lu H, Lin H, Li X, Ni M, Sun H, Li C, Jiang H, Li F, Zhang M, Zhao Y, Zhang Y. Aortic adventitialangiogenesis and lymphangiogenesis promote intimal inflammation andhyperplasia. Cardiovasc Pathol, 2009, 18(5): 269–278

doi: 10.1016/j.carpath.2008.07.004
Qi L H, Wang Y, Gao F, Zhang C, Ding S F, Ni M, Feng J B, Zhang Y. Enhanced stabilization of atherosclerosisplaques in apolipoprotein E-knockout mice by combinatorial Toll-likereceptor 1 and 2 gene silencing. Hum GeneTher, 2009, 20(7): 739–750

doi: 10.1089/hum.2008.203
Qi L H, Wang Y, Zhang C, Ding S F, Ni M, Feng J B, Zhang Y. Combinatorialinterference of Toll-like receptor 2 and 4 remarkably stabilizes atheroscleroticplaque in apolipoprotein E-knockout mice. J Am Coll Cardiol (Abs), 2009, 53, Suppl: A423
Hu Q, Zhang X J, Liu C X, Wang X P, Zhang Y. PPARγ1-induced caveolin-1enhances cholesterol efflux and attenuates atherosclerosis in apolipoproteinE-deficient mice. J Vasc Res, 2010, 47(1): 69–79

doi: 10.1159/000235927
Hu Q, Zhang X J, Zhang C, Zhao Y X, He H, Liu C X, Feng J B, Jiang H, Yang F L, Zhang C X, Zhang Y. Peroxisome proliferator-activated receptor-γ1 genetherapy attenuates atherosclerosis and stabilizes plaques in apolipoproteinE-deficient mice. Hum Gene Ther, 2008, 19(3): 287–299

doi: 10.1089/hum.2007.0142
Wang W, Liu X, Zhao J, Zhao B, Zhang S, Miao J. A novel butyrolactone derivative inhibited apoptosisand depressed integrin beta4 expression in vascular endothelial cells. Bioorg Med Chem Lett, 2007, 17(2): 482–485

doi: 10.1016/j.bmcl.2006.10.023
Wang W, Liu X, Zhang Y, Zhao J, Zhao B, Zhang S, Miao J. Both senescenceand apoptosis induced by deprivation of growth factors were inhibitedby a novel butyrolactone derivative through depressing integrin beta4in vascular endothelial cells. Endothelium, 2007, 14(6): 325–332

doi: 10.1080/10623320701746206
Meng N, Zhao J, Zhao B, Cheng Y, Wang W, Zhang Y, Zhang S, Miao J. A novel butyrolactone derivative inhibitedsmooth muscle cell migration and proliferation and maintained endothelialcell functions through selectively affecting Na, K-ATPase activityand mitochondria membrane potential during in vitro angiogenesis. J Cell Biochem, 2008, 104(6): 2123–2130

doi: 10.1002/jcb.21769
Chen W Q, Zhong L, Zhang L, Ji X P, Zhang M, Zhao Y X, Zhang C, Zhang Y. Oral rapamycin attenuates inflammationand enhances stability of atherosclerotic plaques in rabbits independentof serum lipid levels. Br J Pharmacol, 2009, 156(6): 941–951

doi: 10.1111/j.1476-5381.2008.00102.x
Sun H W, Li C J, Chen H Q, Lin H L, Lv H X, Zhang Y, Zhang M. Involvementof integrins, MAPK, and NF-kappaB in regulation of the shear stress-inducedMMP-9 expression in endothelial cells. Biochem Biophys Res Commun, 2007, 353(1): 152–158

doi: 10.1016/j.bbrc.2006.12.002
Zhang P F, Su H J, Yao G H, Wu W, Zhang M, Liu C X, Jiang H, Ding S F, Zhang C, Zhao Y X, Zhang Y. Plaque volume compression ratio, a novel biomechanicalindex, is independently associated with ischemic cerebrovascular events. J Hypertens, 2009, 27(2): 348–356
Ding S, Zhang M, Zhao Y, Chen W, Yao G, Zhang C, Zhang P, Zhang Y. The role of carotid plaque vulnerabilityand inflammation in the pathogenesis of acute ischemic stroke. Am J Med Sci, 2008, 336(1): 27–31

doi: 10.1097/MAJ.0b013e31815b60a1
Chen W Q, Zhang M, Ji X P, Ding S F, Zhao Y X, Chen Y G, Zhang C, Zhang Y. Usefulness of high-frequency vascularultrasound imaging and serum inflammatory markers to predict plaquerupture in patients with stable and unstable angina pectoris. Am J Cardiol, 2007, 100(9): 1341–1346

doi: 10.1016/j.amjcard.2007.06.044
Zhang Y. Author Reply. Am J Cardiol, 2008, 101(10): 1519

doi: 10.1016/j.amjcard.2008.02.009
Wang Y, Li L, Tan H W, Yu G S, Ma Z Y, Zhao Y X, Zhang Y. Transcoronaryconcentration gradient of sCD40L and hsCRP in patients with coronaryheart disease. Clin Cardiol, 2007, 30(2): 86–91

doi: 10.1002/clc.26
Chen W Q, Zhong L, Zhang L, Ji X P, Zhao Y X, Zhang C, Jiang H, Wu Y L, Zhang Y. Chinesemedicine tongxinluo significantly lowers serum lipid levels and stabilizesvulnerable plaques in a rabbit model. JEthnopharmacol, 2009, 124(1): 103–110

doi: 10.1016/j.jep.2009.04.009
Zhang L, Wu Y, Jia Z, Zhang Y, Shen H Y, Wang X L. Protective effects of a compound herbal extract (TongXin Luo) on free fatty acid induced endothelial injury: implicationsof antioxidant system. BMC Complement AlternMed, 2008, 8: 39

doi: 10.1186/1472-6882-8-39
[1] Jing Zhang,Shan Gao,Zhongping Duan,Ke-Qin Hu. Overview on acute-on-chronic liver failure[J]. Front. Med., 2016, 10(1): 1-17.
[2] Jonathan Skupsky,Ke-Qin Hu. Current hepatitis B treatment guidelines and future research directions[J]. Front. Med., 2014, 8(2): 145-157.
[3] Rui Yu,Rong Fan,Jinlin Hou. Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China[J]. Front. Med., 2014, 8(2): 135-144.
[4] Li Shang, Mingrong Wang. Molecular alterations and clinical relevance in esophageal squamous cell carcinoma[J]. Front Med, 2013, 7(4): 401-410.
[5] Xiangwei Li, Yu Yang, Jianmin Liu, Feng Zhou, Wei Cui, Ling Guan, Fei Shen, Cong Gao, Mufei Li, Qi Jin, Lei Gao. Treatment outcomes of pulmonary tuberculosis in the past decade in the mainland of China: a meta-analysis[J]. Front Med, 2013, 7(3): 354-366.
[6] Yingqi Zhao, Donglin Zeng. Recent development on statistical methods for personalized medicine discovery[J]. Front Med, 2013, 7(1): 102-110.
[7] Salomone Di Saverio, Fausto Catena, Michael D. Kelly, Gregorio Tugnoli, Luca Ansaloni. Severe adhesive small bowel obstruction[J]. Front Med, 2012, 6(4): 436-439.
[8] Jin Gao, Ben Panizza, Newell W. Johnson, Scott Coman, Alan R. Clough. Basic consideration of research strategies for head and neck cancer[J]. Front Med, 2012, 6(4): 339-353.
[9] Zhiyuan Zhang. Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region[J]. Front Med, 2011, 5(4): 401-413.
[10] Sowmya Viswanathan, Armand Keating. Overcoming the challenges of conducting translational research in cell therapy[J]. Front Med, 2011, 5(4): 333-335.
[11] Chun Tang, Baolin Wang, Bing Xie, Hongming Liu, Ping Chen. Treatment of severe acute pancreatitis through retroperitoneal laparoscopic drainage[J]. Front Med, 2011, 5(3): 302-305.
[12] Yiling Wu. Construction of the vessel-collateral theory and its guidance for prevention and treatment of vasculopathy[J]. Front Med, 2011, 5(2): 118-122.
[13] Ranhua JIANG, Zhibo HAN, Guangsheng ZHUO, Xiaodan QU, Xue LI, Xin WANG, Yuankang SHAO, Shimin YANG, Zhong Chao HAN. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study[J]. Front Med, 2011, 5(1): 94-100.
[14] Hao WEN, Tuerganaili AJI, Ying-Mei SHAO, . Diagnosis and management against the complications of human cystic echinococcosis[J]. Front. Med., 2010, 4(4): 394-398.
[15] Shi-Ming CHENG MD, Yu-Ji LAI MS, Er-Yong LIU MS, Lin ZHOU MD, Xue-Jing WANG MS, Qiu-Lan CHEN MS, Dong-Ming LI MS, Ning WANG MD, . Study on factors affecting TB/HIV co-infection in four counties of China[J]. Front. Med., 2010, 4(2): 185-191.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed