Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin

AimsThis study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.Main methodsAPOE null mice at 6 and 15 weeks of age were treated with melatonin at a dose of 0.1 mg/kg/day or 10 mg/kg/day. We evaluated both histopathological alterations in endothelial and vascular smooth muscle cells by CyPA and rolling mononuclear cell expression during the early phase of atherosclerosis development.Key findingsOur study showed that CyPA expression increases and may modulate inflammatory cell adhesion and interleukin-6 expression inducing vascular smooth muscle cell migration and inflammatory cell extravasation in a time-dependent manner. Moreover, we observed an indirect atheroprotective effect of melatonin on vascular injury; it inhibited CyPA mediated inflammatory cell extravasation and oxidative stress.SignificanceThe melatonin treatment may represent a new atheroprotective approach that contributes to reducing the early phase of atherosclerosis involving the rolling of monocytes, their passage to subendothelial space and inhibition of CyPA expression.