Ghrelin suppresses inflammation in HUVECs by inhibiting ubiquitin-mediated uncoupling protein 2 degradation

Abstract

Atherosclerosis is considered the major cause of heart attack, stroke and gangrene of the extremities, which is responsible for 50% of all mortality in Western countries. The pathogenesis and causes of atherosclerosis remain elusive. Recent studies highlight inflammation as a contributing factor for atherosclerosis in all stages of the disease process. In this study, we demonstrate that the treatment of human umbilical vein endothelial cells (HUVECs) with ghrelin inhibits the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response, In addition, treatment with ghrelin led to the accumulation of uncoupling protein 2 (UCP2) in the cells, thus decreasing reactive oxygen species (ROS) generation. Moreover, the siRNA-mediated knockdown of UCP2 expression suggested that the inhibitory effects of ghrelin on the inflammatory response relied on its ability to induce the accumulation of cellular UCP2 levels. Further analysis indicated that the accumulation of UCP2 in the ghrelin-treated cells was due to the ability of ghrelin to inhibit the ubiquitination of UCP2 and prevent UCP2 degradation, resulting in the extended protein half-life of UCP2. On the whole, our data indicate that ghrelin inhibits the oxLDL-induced inflammatory response in HUVECs, and may thus have potential for use as an anti-atherosclerotic agent. Our data may also provide valuable insight into the pathogenesis of atherosclerosis.