Hyperglycemia-induced Oxidative Stress and its Role in Diabetes Mellitus Related Cardiovascular Diseases

Abstract

Diabetes mellitus is associated to an increased risk of cardiovascular diseases. Hyperglycemia is an important factor in cardiovascular damage, working through different mechanisms such as activation of protein kinase C, polyol and hexosamine pathways, advanced glycation end products production. All of these pathways, in association to hyperglycemia-induced mitochondrial dysfunction and endoplasmic reticulum stress, promote reactive oxygen species (ROS) accumulation that, in turn, promote cellular damage and contribute to the diabetic complications development and progression. ROS can directly damage lipids, proteins or DNA and modulate intracellular signaling pathways, such as mitogen activated protein kinases and redox sensitive transcription factors causing changes in protein expression and, therefore, irreversible oxidative modifications. Hyperglycemia-induced oxidative stress induces endothelial dysfunction that plays a central role in the pathogenesis of micro- and macro-vascular diseases. It may also increase pro-inflammatory and pro-coagulant factors expression, induce apoptosis and impair nitric oxide release. Oxidative stress induces several phenotypic alterations also in vascular smooth-muscle cell (VSMC). ROS is one of the factors that can promote both VSMC proliferation/migration in atherosclerotic lesions and VSMC apoptosis, which is potentially involved in atherosclerotic plaque instability and rupture. Currently, there are contrasting clinical evidences on the benefits of antioxidant therapies in the prevention/treatment of diabetic cardiovascular complications. Appropriate glycemic control, in which both hypoglycemic and hyperglycemic episodes are reduced, in association to the treatment of dyslipidemia, hypertension, kidney dysfunction and obesity, conditions which are also associated to ROS overproduction, can counteract oxidative stress and, therefore, both microvascular and macrovascular complications of diabetes mellitus.

Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats

“…Hyperglycemia activates protein kinase C (PKC) and Poly-ADP ribose polymerase (PARP) pathways; it also enhances formation of advanced glycation end products (AGEs) and polyol and hexosamine pathways. These pathways are activated or enhanced due to mitochondrial superoxide overproduction (12).…”

Coronary Risk Estimation according to the Framingham-Wilson Score and Impaired Fasting Glucose in Adult Subjects from Maracaibo city, Venezuela

“…Assessment of coronary risk by gender in each glycemic status group revealed that IFG men have a significantly higher risk than their female counterparts, similar to previous results from Modrego et al [47]; however, it should be noted that coronary risk remained similar between genders among diabetics, demonstrating the role of T2DM as a gender-independent cardiovascular risk factor [48]. Although the presence of IFG has been associated with increased cardiovascular risk through its association with comorbities such as dyslipidemia and hypertension [49], several studies have proposed possible mechanisms which chronic IFG may trigger endothelial dysfunction, or at least, play a role in atherogenesis by increasing production of reactive oxygen species [50], advanced glycation endproducts [51], and inducing low-grade inflammation [52]. Likewise, elements such as physical inactivity, lipid-rich and carbohydraterich diets have been linked with prediabetic states [53], yet few studies explore the relationship of these sociodemographic aspects with cardiovascular risk.…”

Investigation of DNA repair genes XPD and hOGG1 in type 2 Diabetes mellitus

“…Chronic hyperglycemia causes oxidative stress [10], which is also associated with progression of T2DM and several diabetic complications [11]. The accumulation of ROS lead to modifications that cause DNA damage on nuclear and mitochondrial DNA [12].…”