title: Angiotensin II Destabilizes Coronary Plaques in Watanabe Heritable Hyperlipidemic Rabbits.
abstract: Increased plasma concentrations of angiotensin II (Ang II) have been implicated in many cardiovascular diseases, such as atherosclerosis, aortic aneurysms, and myocardial infarction, in humans. However, it is not known whether high levels of plasma Ang II affect coronary plaque stability and subsequent myocardial infarction. This study was designed to examine whether elevated plasma Ang II can directly induce coronary events, such as acute coronary syndrome.
  
  
  
  To examine the above hypothesis, we infused Ang II (100 ng/min per kg [low group] and 200 ng/min per kg [high group]) or saline vehicle via osmotic minipumps into Watanabe heritable hyperlipidemic rabbits, a model of human familial hypercholesterolemia and atherosclerosis. Infusion of Ang II resulted in mortality rates of 50% and 92% in the low- and high-Ang II groups, respectively, whereas there were no deaths in the vehicle group. Pathological analysis revealed that Ang II-infused Watanabe heritable hyperlipidemic rabbits that died showed myocardial infarction. Furthermore, Ang II-infused Watanabe heritable hyperlipidemic rabbits exhibited coronary plaque erosion and rupture that were associated with thrombosis.
  
  
  
  These findings suggest that increased blood levels of Ang II can destabilize coronary plaques and trigger the thrombosis, which possibly induces myocardial infarction. The model described in this study provides a novel means for the study of human acute coronary syndrome.
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Ning
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Dedong
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xi'an Medical University, Xi'an, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Ahmed Bilal
authors.initials: AB
authors.lastname: Waqar
authors.affiliation: Research Institute of Atherosclerotic Disease and Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000818:Animals; D003324:Coronary Artery Disease / Q000235:genetics / Q000473:pathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000235:genetics; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011817:Rabbits; D013997:Time Factors
chemical_list: D000804:Angiotensin II
keywords: acute coronary syndrome; angiotensin II; hypercholesterolemia; myocardial infarction; thrombosis