Ghrelin ameliorates atherosclerosis by inhibiting endoplasmic reticulum stress

The effects of ghrelin, a peptide hormone, on atherogenesis are mainly beneficial. This study aimed to investigate whether ghrelin ameliorates atherosclerosis (AS) by preventing endoplasmic reticulum stress (ERS). AS was induced by a high-fat diet in ApoE^-/- mice. AS lesions in aortas were detected by Oil Red O staining, and the inner diameter and intima-media thickness (IMT) of the abdominal aorta were analyzed by ultrasonography. The protein expression of the ERS markers, 78-kDa glucose-regulated protein, C/EBP homologous protein, and active caspase-12, was detected by Western blot analysis. High-fat diet-fed ApoE^-/- mice showed AS lesions and increased aortic IMT. Ghrelin ameliorated these findings. Moreover, the protein expression of ERS markers was upregulated in the AS aorta and downregulated by ghrelin treatment. The above beneficial effects of ghrelin on AS and ERS were blocked by the ERS inducer, tunicamycin. In rat aortic endothelial cells, oxidized low-density lipoprotein and tunicamycin triggered ERS, which could be inhibited by ghrelin pretreatment. These results suggest that ghrelin can ameliorate activation of ERS, which may be the beneficial effect of ghrelin on AS. Ghrelin may be a new target and strategy for prevention and therapy of AS.