Hyperglycemia Aggravates Diet-Induced Coronary Artery Disease and Myocardial Infarction in SR-B1-Knockout/ApoE-Hypomorphic Mice

Abstract

Diabetes is a risk factor for development of atherosclerotic cardiovascular disease. Animal model studies in mice revealed that hyperglycemia increases development of atherosclerosis in the aorta as well as myocardial fibrosis in surgical models of coronary artery ligation; however, the impact of hyperglycemia on coronary artery atherosclerosis and subsequent heart disease is less clear. To investigate the effect of hyperglycemia on atherosclerosis and coronary heart disease, we used a mouse model of diet-induced coronary artery atherosclerosis and myocardial infarction, the high fat/high cholesterol (HFC) diet fed SR-B1 knockout (KO)/apoE-hypomorphic (HypoE) mouse. Hyperglycemia was induced in these mice by streptozotocin (STZ) treatment. This increased HFC diet-dependent atherosclerosis development (p = 0.02) and necrotic core formation (p = 0.0008) in atherosclerotic plaques in the aortic sinus but did not increase the extent of atherosclerosis in coronary arteries. However, it did increase the extent of platelet accumulation in atherosclerotic coronary arteries (p = 0.017). This was accompanied by increased myocardial fibrosis (p = 0.005) and reduced survival (p = 0.01) compared to control-treated, normoglycemic mice. These results demonstrate that STZ-treatment exerted differential effects on the level of atherosclerosis in the aortic sinus and coronary arteries. These results also suggest that SR-B1-KO/HypoE mice may be a useful non-surgical model of diabetic cardiomyopathy in the context of coronary artery atherothrombosis.

Brahma-Related Gene 1 Deficiency in Endothelial Cells Ameliorates Vascular Inflammatory Responses in Mice

“…these mice seems to be associated with myocardial infarction and resulting cardiac conduction and functional abnormalities (Nakatsu et al, 2017;Wang Q. et al, 2017;Gonzalez et al, 2018). However, these associations still need to be further investigated.…”

Animal models of human atherosclerosis: current progress

“…This model is of specific interest due to the lack of small animal models resembling severe atherosclerosis symptoms (formation of advanced plaques), severe coronary heart disease, and even premature death seen in humans (59,60).…”

Scavenger Receptor Class B type 1 (SR-B1) and the modifiable risk factors of stroke

“…Whereas, type II diabetics are more likely to have obesity, peripheral arterial disease, history of transient ischemic attack, and stroke attributable to large-artery atherosclerosis [89]. In a recent study, Gonzalez et al [60] used streptozocin to induce hyperglycemia in SR-B1-knockout/hypoE mice. They reported that the SR-B1-knockout/hypoE hyperglycemic mice had an increased incidence of coronary artery atherothrombosis, myocardial infarction, and early death when on a high-fat, high-cholesterol diet [60].…”

“…In a recent study, Gonzalez et al [60] used streptozocin to induce hyperglycemia in SR-B1-knockout/hypoE mice. They reported that the SR-B1-knockout/hypoE hyperglycemic mice had an increased incidence of coronary artery atherothrombosis, myocardial infarction, and early death when on a high-fat, high-cholesterol diet [60]. SR-B1 was increased in type 2 diabetes patients, but not in those with hypercholesterolemia [90].…”