Melatonin attenuates inflammation-related venous endothelial cells apoptosis through modulating the MST1-MIEF1 pathway.

Chronic venous disease (CVD) is a prevalent and potentially debilitating condition that affects millions of individuals. An excessive endothelial inflammatory response is reportedly involved in the development of CVD. In this study, we explored the effect and mechanism of melatonin on venous endothelial damage induced by tumor necrosis factor α (TNF-α). Our data demonstrated that inflammation injury triggered mitochondrial dysfunction, activated reactive oxygen species-related oxidative damage, inhibited mitochondrial potential and ultimately initiated caspase-involved cellular death. Interestingly, melatonin preserved inflammation-attacked mitochondrial performance and thus increased cell survival under TNF-α. Cellular experiments illustrated that inflammation injury promoted the levels of mammalian sterile 20-like kinase 1 (MST1) and mitochondrial elongation factor 1 (MIEF1); active MST1-MIEF1 pathway disturbed mitochondria-related energy production, leading to mitochondria-induced cell damage. Interestingly, melatonin effectively suppressed MST1-MIEF1 axis and thus improved cell survival ratio under TNF-α-mediated inflammation injury. Reactivation of MST1-MIEF1 pathway attenuated melatonin-related endothelial protective actions. Herein, our results illuminate that melatonin is an effective approach to attenuate inflammation-related venous endothelial cell damage through handling the MST1-MIEF1 signaling pathway.