Mouse models of plaque rupture.
OBJECTIVE
Atherosclerotic plaque destabilization and rupture is an important pathological condition that may account for approximately 70% of acute myocardial infarction cases. To analyse the mechanisms by which an atherosclerotic plaque destabilizes and ruptures and examine the effects of novel therapeutic approaches, several groups have developed mouse models of plaque rupture.


RESULTS
Findings from intracoronary imaging modalities support the role of rupture-prone 'vulnerable plaques' characterized by pathological studies as precursors of plaque rupture and acute myocardial infarction. Atherosclerotic plaques in the brachiocephalic arteries of apolipoprotein E (ApoE)-deficient mice fed a high-fat diet demonstrate several key histological features of ruptured human plaques. Angiotensin II infusion accelerates plaque destabilization and rupture, which has enabled researchers to analyse the role of pathophysiological and genetic factors that accelerate plaque destabilization and rupture and qualitatively examine the effects of experimental therapies. The plaque rupture model in the brachiocephalic arteries of ApoE-deficient mice is disputed due to dissimilarities from human plaques regarding the incidence of thrombotic occlusion and computer-simulated mechanical stress in the plaque.


CONCLUSIONS
Although no mouse model examined completely simulates the entire process of plaque rupture, the brachiocephalic artery in ApoE-deficient mice fed a high-fat diet, with or without angiotensin II infusion, is a practically feasible model for plaque rupture.
Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Tetsuya
T
Matoba
Kei
K
Sato
Kensuke
K
Egashira
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D001057:Apolipoproteins E; D004041:Dietary Fats