Atherosclerotic Plaque Stability in Aged ApoE-/-/SOD2+/- Mice: The Role of Calpain 1 and 2 (2015)
Undergraduates: Samthosh Alahari, Aleksandr Vendrov; Marschall S. Runge
Faculty Advisor: Nageswara Madamanchi
Department: Business Administration
Atherosclerotic cardiovascular disease is the leading cause of mortality in developed countries. Plaque made of cholesterol, fat, and fibrin builds up in atherosclerotic arteries, which may partially or totally block blood flow causing myocardial infarction and stroke. Apolipoprotein E-deficient (ApoE-/-) mice are a model of atherosclerosis exhibiting elevated cholesterol levels, oxidative stress and a propensity to develop aortic atherosclerosis. Superoxide dismutase 2 (SOD2), a mitochondrial matrix enzyme, converts superoxide radicals into less toxic hydrogen peroxide and protects against oxidative stress and atherosclerosis. Aortic atherosclerosis is greater in ApoE-/-/SOD2+/- compared with ApoE-/- mice and increases with aging. SOD2 deficiency increases apoptosis of vascular smooth muscle cells (VSMC) in the atherosclerotic fibrous cap which increases the risk of plaque rupture and thrombosis, causing myocardial infarction and stroke. Calpain 1 and 2 proteases promote VSMC apoptosis. We observed increased Calpain 1 and 2 expression in the aortas of aged ApoE-/-/SOD2+/- mice versus young ApoE-/- mice, which is correlated with increased VSMC apoptosis in the fibrous cap and greater predisposition for plaque rupture. A better understanding of this relationship might lead to new therapeutic strategies to prevent atherosclerosis complications in aging.