The role of gasotransmitters NO, H S, CO in myocardial ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning

Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide. The development of cardioprotective therapeutic agents remains a partially unmet need and a challenge for both medicine and industry, with significant financial and social implications. Protection of the myocardium can be achieved by mechanical vascular occlusions such as preconditioning (PC) when brief episodes of ischemia/reperfusion are subjected prior to ischemia; postconditioning (PostC) when the brief episodes are subjected at the immediate onset of reperfusion, as well as remote conditioning (RC) when the brief episodes are subjected in another vascular territory. The elucidation of the signaling pathways which underlie the protective effects of PC, PostC and RC would be expected to reveal novel molecular targets for cardioprotection that could be manipulated by pharmacological agents to prevent reperfusion injury. Gasotransmitters including nitric oxide (NO), hydrogen sulphide (H2 S) and carbon monoxide (CO) are a growing family of regulatory molecules which impact on physiological and pathological functions. NO, H2 S and CO share several common properties; they are beneficial at low concentrations but hazardous in higher amounts, they relax smooth muscle cells, inhibit apoptosis, and exert anti-inflammatory effects. In the cardiovascular system, both NO, H2 S and CO induce vasorelaxation, and promote cardioprotection. In this review article, we summarize current knowledge on the role of the gasotransmitters NO, H2 S, and CO in myocardial ischemia/reperfusion injury and cardioprotection provided by conditioning strategies and highlight future perspectives in cardioprotection by NO, H2 S, CO, as well as their donor molecules