Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes

Abstract

Physical inactivity and sedentary lifestyle contribute to the widespread epidemic of obesity among both adults and children leading to rising cases of diabetes. Cardiovascular disease complications associated with obesity and diabetes are closely linked to insulin resistance and its complex implications on vascular cells particularly endothelial cells. Endoplasmic reticulum (ER) stress is activated following disruption in post-translational protein folding and maturation within the ER in metabolic conditions characterized by heavy demand on protein synthesis, such as obesity and diabetes. ER stress has gained much interest as a key bridging and converging molecular link between insulin resistance, oxidative stress, and endothelial cell dysfunction and, hence, represents an interesting drug target for diabetes and its cardiovascular complications. We reviewed here the role of ER stress in endothelial cell dysfunction, the primary step in the onset of atherosclerosis and cardiovascular disease. We specifically focused on the contribution of oxidative stress, insulin resistance, endothelial cell death, and cellular inflammation caused by ER stress in endothelial cell dysfunction and the process of atherogenesis.

Periodontitis and Tooth Loss Have Negative Systemic Impact on Circulating Progenitor Cell Levels: A Clinical Study

“…Moreover, another study on 22 healthy adults with moderate to severe periodontitis who underwent complete mouth disinfection found that, at one-month follow-up, periodontal treatment resulted in significant improvements in periodontal pocketing, flow-mediated dilation, and serum IL-6, as well as a trend toward reduction in serum CRP [46]. Furthermore, several studies have reported that an intensive periodontal treatment resulted not only in a temporary increase in serum levels of CRP and IL-6, but also in a significant improvement of endothelial dysfunction indexes at six months after active periodontal therapy [47][48][49].…”

Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis

“…It is also the site for steroid, cholesterol and lipid synthesis. Under pathological conditions, inflammation induced by hypoxia, hyperglycemia and oxidative stress can lead to accumulation of unfolded or misfolded proteins in the endoplasmic reticulum, which will trigger a series of intracellular stress responses, called endoplasmic reticulum stress (ERS) [7]. Glucose regulated protein 78 (GRP78) is the feeling molecular for ER homeostasis.…”

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

“…CVD are the leading cause of death in the world. These diseases affect the structure and/or function of the heart and blood vessels, and include highly prevalent disorders such as hypertension, atherosclerosis and myocardial infarction, among others [1,4,109,110]. Several metabolic risk factors involved in the development of CVD, such as hypercholesterolemia and diabetes promote EC dysfunction [4,109,111]…”

“…Atherogenesis begins with the loss of integrity of the vascular endothelium or endothelial dysfunction, and its progression leads to vessel damage and occlusion that may result in a variety of outcomes, such as thrombosis of the arterial wall, as well as injury and dysfunction of tissues and organs [2,3]. Numerous studies have acknowledged the crucial role of endothelial dysfunction in CVD, so it is necessary to find an optimal model for research of this disease [2,[4][5][6].…”