Pathogenesis and pathophysiology of accelerated atherosclerosis in the diabetic heart

Abstract

It has been established that atherosclerotic coronary artery disease is more frequent and more severe in diabetic compared to non-diabetic subjects, but the reason for the excess risk of developing coronary macroangiopathy in diabetes remains incompletely characterized. Various biochemical mechanisms speculated to being at the "heart" of diabetic cardiac and coronary macroangiopathy are reviewed in the present article. In doing so, this article presents evidence that the labyrinthine interactions of hyperglycemia, insulin resistance, and dyslipidemia in diabetes result in a pro-atherogenic phenotype. Furthermore, the diabetic milieu yields a complex (dys)metabolic environment characterized by chronic inflammation, procoagulability, impaired fibrinolysis, neovascularization abnormalities, and microvascular defects that cumulatively alter blood rheology, artery structure, and homeostasis of the endothelium. The contributory influences of these factors in the pathophysiology of coronary artery disease in diabetes are also discussed.

Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways

“…In addition, they lend further support to the notion that mitochondria represent a viable target for future therapies directed at ameliorating heart failure and other comorbidities that come with diabetes. diabetes; mitochondria; apoptosis THE PATHOGENIC MECHANISMS by which persistent hyperglycemia and dyslipidemia in diabetes adversely affect the coronary vasculature are well characterized (21), but the mechanisms by which diabetes creates a progressively degenerative state within the myocardium are not as clear. Recently, investigators have focused on the role of myocardial cell death because of the increasing number of studies demonstrating high levels of apoptotic and necrotic cardiomyocytes in experimental models of diabetes (4,23,27) and in cardiac tissue from diabetic patients (14,25,37).…”

Mechanism of the beneficial and protective effects of exenatide in diabetic rats

“…Type 1 and type 2 DM (T1DM and T2DM) can lead to a deficiency in T1DM or insulin resistance or a combination of both in T2DM, resulting in prolonged hyperglycaemia, hyperlipidaemia and exaggerated levels of reactive oxygen species (ROS) with an impaired antioxidant defence system (D'Souza et al 2009, Figueroa-Quevedo & Agil 2011.…”

Glycolaldehyde Induces Oxidative Stress in the Heart: A Clue to Diabetic Cardiomyopathy?

“…Heart disease in DM affects function at different levels, promoting angiopathy and cardiomyopathy [1]. Type II diabetic patients with coronary artery disease, which causes the occlusion of the arteries that supply the heart, display more severe coronary atherosclerosis than non-diabetic subjects [2].…”