Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models?

Abstract

Diabetes mellitus is associated with a greater risk of developing atherosclerosis and its complications: stroke, myocardial infarction, and peripheral vascular disease. In patients with diabetes, atherosclerosis represents a complex multifactorial disease with increased lesion progression and severity compared to the nondiabetic population. Several risk factors have been proposed to explain the increased risk of cardiovascular disease with diabetes. They include: hyperglycaemia, dyslipidemia, accelerated formation of advanced glycation end-products (AGEs), increased oxidative stress, and genetic factors. It is difficult to precisely establish the elements leading to diabetes-accelerated atherosclerosis by means of epidemiological studies because all these factors coexist in diabetic patients. Thus, diabetic animal models that reproduce exacerbation of atherosclerosis would be helpful to understand why atherosclerosis is accelerated by diabetes, and to design appropriate treatments to limit its progression. This review analyzes most of the animal models developed to reproduce diabetes-accelerated atherosclerosis, and summarizes the effects of hyperglycaemia and lipid abnormalities on atherogenesis.