Oxidative stress-related biomarkers in essential hypertension and ischemia-reperfusion myocardial damage

Abstract

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers.

Figure 1

Cellular response to reactive oxygen species. Several pathophysiological conditions determine an increase on intracellular ROS levels. Transcription factor induction is dependent in the ROS levels. Low to moderate ROS levels induce Nrf-2 activation which increases the expression of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, NADPH:quinone oxidoreductase 1, and heme oxygenase-1 while high levels of ROS induce NF-κB activation, which trigger a proinflammatory response characterized by increased levels of TNF-α, IL-1β, IL-6, and IL-8, increased expression of adhesion molecules, such as E-selectin, VCAM-1, and ICAM-1, and promotion of oxidative stress. AA: arachidonic acid; CAT: catalase; GSH-Px: glutathione peroxidase; GSR: glutathione reductase; glutathione S-transferase: GSTs; HO-1: heme oxygenase-1; NADPH:quinone oxidoreductase 1: NQO1; IL-1 β: Interleukin 1β; IL-6: Interleukin 6; IL-8: Interleukin 8; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf-2: nuclear factor- (erythroid-derived 2-) like 2.