Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Abstract

Murine coronary arteries are very resistant to the development of atherosclerosis, which may be related to their intramyocardial course. Blood pressure promotes atherosclerotic plaque formation by acting as a physical force that potentiates the migration of pro-atherogenic lipoproteins across the endothelium. C57BL/6N apolipoprotein (apo) E deficient mice have increased remnant lipoproteins that are a risk factor for coronary atherosclerosis. In this study, our aim was to quantify coronary atherosclerosis and artery remodeling following transverse aortic constriction (TAC) in C57BL/6N apo E−/− mice and to evaluate the impact of increased remnant lipoproteins on the development of pressure overload-induced cardiac hypertrophy and heart failure. Advanced atherosclerotic lesions were observed in the left coronary artery of C57BL/6N apo E−/− TAC mice but not in C57BL/6N TAC mice. Pressure overload resulted in markedly increased cardiac hypertrophy and more pronounced heart failure in C57BL/6N apo E−/− TAC mice in comparison to C57BL/6N TAC mice. Pathological hypertrophy, as evidenced by increased myocardial fibrosis and capillary rarefaction, was more prominent in C57BL/6N TAC apo E−/− than in C57BL/6N TAC mice and led to more marked cardiac dysfunction. In conclusion, TAC in apo E deficient mice induces coronary atherosclerosis and aggravates the development of pathological cardiac hypertrophy and heart failure.

Overview of the Most Popular Currently Used Murine Models of Atherosclerosis

“…This suggests that a 50% decrease in ApoE is inadequate to trigger an elevation in plasma cholesterol. No difference was observed between mice of different age or sex (Muthuramu et al, 2022).…”

“…From the age of six weeks onwards, there is observable adherence of monocytes to the endothelium and after eight weeks, the development of foam cell lesions begins. By 15-20 weeks, mediumsized lesions and fibrous plaques primarily composed of smooth cells, extracellular matrix, as well as plaques with a necrotic core and a fibrous cap can be identified (Muthuramu et al, 2022). In later stages, fibrous niduses containing lipids are formed which soon become calcified.…”