Biomechanical Modeling of Atherosclerotic Lesions in ApoE Deficient Mice

Cardiovascular disease remains the principal killer in the western world despite major advances in treatment of its patients [1]. It is generally accepted that sudden rupture of vulnerable plaque followed by thrombus formation underlies most cases of myocardial infarction and is responsible for more than a half of 500,000 coronary heart disease deaths every year. Although histopathological analysis of postmortem specimens have provided important data on histological features of ruptured human plaques, there is an urgent need for good representative animal models of plaque rupture. Over the last decade and a half, genetically engineered mice have been widely used to study the pathogenesis and potential treatment of atherosclerotic lesions, as well as genetic, hormonal and environmental influences on development of atherosclerosis. Though many of the features of plaque development and progression that occur in human plaques are similarly observed in murine plaques, these mouse models have long been regarded as poor models to study plaque rupture because the aortic sinus lesions seldom show any signs of fibrous cap disruption. Several recent studies reported potentially unstable atherosclerotic lesions in older apoE-deficient mice in another anatomic site, the proximal part of the brachiocephalic artery (BCA) [2, 3]. The unusual stability of aortic lesions compared to the BCA lesions in ApoE knockout mice is an unexplained paradox in developing a mouse model of plaque rupture. In this paper, we use histology based finite element analysis to evaluate peak circumferential stresses in aortic and BCA lesions from high fat fed ApoE KO mice.