Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.
Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis--often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.
Department of Medicine, Division of Cardiovascular Medicine, University of Nevada, Las Vegas, NV, USA.
Oliver G
OG
Abela
Department of Medicine, Division of Cardiovascular Medicine, University of Nevada, Las Vegas, NV, USA.
Chowdhury H
CH
Ahsan
Division of Cardiovascular Medicine, Michigan State University, East Lansing, MI, USA.
Fadi
F
Alreefi
Department of Medicine, Michigan State University, East Lansing, MI, USA.
Negar
N
Salehi
Division of Cardiovascular Medicine, Michigan State University, East Lansing, MI, USA.
Imran
I
Baig
Division of Cardiovascular Medicine, Michigan State University, East Lansing, MI, USA.
Abed
A
Janoudi
Division of Cardiovascular Medicine, Michigan State University, East Lansing, MI, USA. george.abela@ht.msu.edu.|Department of Physiology, Division of Pathology, Michigan State University, East Lansing, MI, USA. george.abela@ht.msu.edu.|Michigan State University, B208 Clinical Center, East Lansing, MI, 48824, USA. george.abela@ht.msu.edu.
George S
GS
Abela
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011817:Rabbits; D012422:Rupture, Spontaneous / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013927:Thrombosis / Q000473:pathology*; D017539:Tunica Intima / Q000473:pathology
Atherosclerosis; Cholesterol crystals; Inflammation; Plaque rupture; Rabbit model