H(2)S Pretreatment Is Promigratory and Decreases Ischemia/Reperfusion Injury in Human Microvascular Endothelial Cells

Endothelial cell injury and vascular function strongly correlate with cardiac function following ischemia/reperfusion injury. Several studies indicate that endothelial cells are more sensitive to ischemia/reperfusion compared to cardiomyocytes and are critical mediators of cardiac ischemia/reperfusion injury. H(2)S is involved in the regulation of cardiovascular system homeostasis and can act as a cytoprotectant during ischemia/reperfusion. Activation of ERK1/2 in endothelial cells after H(2)S stimulation exerts an enhancement of angiogenesis while its inhibition significantly decreases H(2)S cardioprotective effects. In this work, we investigated how H(2)S pretreatment for 24 hours prevents the ischemia/reperfusion injury and promotes angiogenesis on microvascular endothelial cells following an ischemia/reperfusion protocol in vitro, using a hypoxic chamber and ischemic buffer to simulate the ischemic event. H(2)S preconditioning positively affected cell viability and significantly increased endothelial cell migration when treated with 1 μM H(2)S. Furthermore, mitochondrial function was preserved when cells were preconditioned. Since ERK1/2 phosphorylation was extremely enhanced in ischemia/reperfusion condition, we inhibited ERK both directly and indirectly to verify how H(2)S triggers this pathway in endothelial cells. Taken together, our data suggest that H(2)S treatment 24 hours before the ischemic insult protects endothelial cells from ischemia/reperfusion injury and eventually decreases myocardial injury.