Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes

Simple Summary The progressive nature of type 2 diabetes mellitus (T2DM) leads to micro- and macro-vascular complications, including renal and cardiovascular disease. These alone, or in combination, are a major cause of premature morbidity and mortality in diabetic patients. Despite advances in glucose lowering treatments, these diabetic complications are still inadequately prevented or reversed. This ongoing cardiovascular-renal burden in diabetes poses a heavy cost on the health care system. Therefore, there is an urgent need to develop more effective treatments. In this review, we discuss how oxidative stress and inflammation induce and perpetuate the renal and cardiovascular complications of diabetes. It is particularly important to understand these driving mechanisms in order to elucidate pharmacological targets and mechanism-based future drug therapies. Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.

Automated summary

The progressive nature of type 2 diabetes mellitus leads to micro- and macro-vascular complications, including renal and cardiovascular disease, which are major causes of premature morbidity and mortality in diabetic patients. Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, and emerging therapies target these crucial pathways to alleviate the burden of the diseases.