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Front. Physiol. | doi: 10.3389/fphys.2018.01398

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

Leticia Gonzalez1, Melissa E. MacDonald1 and  Bernardo L. Trigatti1*
  • 1McMaster University, Canada

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 diet-fed SR-B1 knockout/apoE-hypomorphic mouse. Hyperglycemia was induced in these mice by streptozotocin treatment. This increased high fat/high cholesterol 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 streptozotocin-treatment exerted differential effects on the level of atherosclerosis in the aortic sinus and coronary arteries. These results also suggest that SR-B1-knockout/apoE-hypomorphic mice may be a useful non-surgical model of diabetic cardiomyopathy in the context of coronary artery atherothrombosis.

Keywords: Atherosclerosis, coronary artery, diabetes, Fibrosis, Hyperglycemia, Myocardial Infarction

Received: 27 Apr 2018; Accepted: 13 Sep 2018.

Edited by:

Francesco Visioli, IMDEA Alimentación, Spain

Reviewed by:

Gilbert R. Thompson, Imperial College London, United Kingdom
Rinke Stienstra, Wageningen University & Research, Netherlands  

Copyright: © 2018 Gonzalez, MacDonald and Trigatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Bernardo L. Trigatti, McMaster University, Hamilton, L8L 2X2, ON, Canada,