Role of Differential Signaling Pathways and Oxidative Stress in Diabetic Cardiomyopathy

Abstract

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemia-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Diabetes-mediated biochemical changes show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. This review focuses on the oxidative stress and signaling pathways in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

“…Increase in oxidative stress-derived inflammation has been hypothesized to be a major mechanism in the pathogenesis and progression of type 2 diabetes (13). Studies have shown that an enhancement in oxidative stress jeopardizes function and structure of myocardium through mechanisms such as microvascular injury, abnormalities in calcium homeostasis, and endothelial dysfunction (40). In this study, we observed that voluntary exercise prevented an increase in myocardial lipid peroxidation and attenuated a decrease in antioxidant enzymes' activity in type 2 diabetic rats.…”

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

“…Therefore, excessive ROS represent critical and central mediators of the complicated cascades associated with myocardial cell apoptosis in the setting of DCM. It is believed that hyperglycemia either directly or indirectly participates in ROS production via glucose autoxidation, alterations in the sorbitol (polyol) pathway, the formation of advanced glycation end products (AGEs), and the activation of both protein kinase C (PKC) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase [42,43] . More importantly, a previous in vitro study demonstrated that high glucose concentrations induce TLR-4 expression via PKC by stimulating NADPH oxidase [44] .…”

GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats

“…Lipid overload results in the accumulation of lipid intermediates, such as diacylglycerol (DAG), which activate protein kinase C (PKC) [4] and the production of reactive oxygen species (ROS) [5,6], which can promote apoptosis [7]. Activation of PKC, oxidative stress and myocardial apoptosis are implicated in diabetes-induced cardiovascular complications [8,9].…”