Hexarelin attenuates atherosclerosis via inhibiting LOX-1-NF-κB signaling pathway-mediated macrophage ox-LDL uptake in ApoE-/- mice

Peptides
Xiu-Li ChengJi-Min Cao

Abstract

Growth hormone secretagogues (GHS) have been proved to exert protective effects on the cardiovascular system, while their potential beneficial effects on macrophages in atherosclerosis (AS) are rarely been clarified. This study aimed to demonstrate whether hexarelin, a synthetic peptidyl GHS, can suppress AS progression via regulating the function of macrophages. AS was induced by chronic (3 months) feeding with high lipid diet in ApoE-/- mice. Mice were treated either with hexarelin (100 μg/kg s.c., q.d. for 3 months) (AS + Hex group) or saline (AS group). Age-matched C57BL/6 J mice were used as normal controls. AS and related signaling molecules in aortic tissues and RAW264.7 macrophages were identified with variant methods including histological staining, ELISA, western blotting, confocal microscopy and flow cytometry. AS significantly developed in ApoE-/- mice fed with high lipids diet. Hexarelin decreased serum TC, TG and LDL-c, increased serum HDL-c and attenuated the formation of atherosclerotic plaques and neointima compared with the AS group. Hexarelin decreased the aortic expressions of CD68 and LOX-1 which were elevated in the AS group. Hexarelin increased GHSR expression, suppressed ox-LDL uptake and LOX-1 expressio...Continue Reading

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