Molecular basis of cardioprotective effect of antioxidant vitamins in myocardial infarction

Abstract

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage.

Figure 1

Schema representing the time course of the effects of ischemia reperfusion. Upon reperfusion there is an oxidative burst, which corresponds to a marked increase in infarct size. Counteracting this process could account for a decrease of up to 50% infarct size.

Figure 2

Hypothesis accounting for the acute myocardial infarct size occurring in ischemia-reperfusion through molecular models based on the role of oxidative stress. Abrogation of the deleterious processes by vitamins C and E. Arrow color code: blue stands for “promotion”; yellow for “inhibition”: mPTP mitochondrial permeability transition pore; NO; nitric oxide; eNOS; endothelial nitric oxide synthase; NADPH, reduced nicotinamide adenine dinucleotide phosphate; NADPH ox, oxidized nicotinamide adenine dinucleotide phosphate; Nrf2, nuclear factor (erythroid-derived 2)-like 2. Adapted from [15], with permissions.