title: Tandem Stenosis to Induce Atherosclerotic Plaque Instability in the Mouse.
abstract: Despite the number of animal models of atherosclerosis, a major limitation in research on mechanisms of plaque rupture is the lack of appropriate atherosclerotic mouse models where lesions develop and progress to a vulnerable and thus rupture-prone phenotype that is typically observed in humans. Most animal models of atherosclerosis typically represent a few but not the full combination of the characteristics seen in human unstable/ruptured plaques. Such characteristics most importantly include a thin and ruptured fibrous cap, plaque inflammation, neovascularization within the plaque (vasa vasorum), plaque hemorrhage, and intravascular (often occlusive) thrombus formation. Ideally, an animal model of plaque instability/rupture would respond to current pharmacological interventions known to reduce the risk of plaque rupture, such as statins. Here we describe a mouse model of plaque instability/rupture that is based on the surgical introduction of a tandem stenosis in the carotid artery. This model results in the formation of unstable atherosclerotic plaques that reflect human plaque pathology. It will allow to further understanding of plaque instability/rupture, to identify the participating factors such as specific proteins, genes and microRNAs, and to develop imaging methods towards the detection of vulnerable, rupture-prone atherosclerotic plaques.
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, St Kilda Road Central, 6492, Melbourne, VIC, 8008, Australia.|Departments of Medicine and Immunology, Monash University, Melbourne, VIC, Australia.
authors.forename: Yung Chih
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, St Kilda Road Central, 6492, Melbourne, VIC, 8008, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, St Kilda Road Central, 6492, Melbourne, VIC, 8008, Australia. karlheinz.peter@bakeridi.edu.au.|Departments of Medicine and Immunology, Monash University, Melbourne, VIC, Australia. karlheinz.peter@bakeridi.edu.au.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology / Q000601:surgery*; D016893:Carotid Stenosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D012422:Rupture, Spontaneous; D013045:Species Specificity; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E
keywords: Acute myocardial infarction; Angiogenesis animal models of human disease; Arterial thrombosis; Atherosclerosis; Gene expression profiling; Inflammation; MicroRNA profiling; Plaque rupture