AMPK activity is down-regulated in endothelial cells of GHS-R(-/-) mice.

Ghrelin/GHS-R axis is known as its role in stimulating growth hormone release. Besides, it is also implicated in the regulation of atherosclerosis (AS), a chronic vascular disease that has been recognized as the main cause of coronary heart disease and cerebrovascular disease. It has been reported that both Ghrelin and AMPK play protective roles in AS by inhibiting the inflammatory response as well as cell proliferation. However, it remains unclear whether AMPK pathway is involved in Ghrelin/GHS-R-mediated inhibition of the inflammatory response and cell proliferation in AS. Here, we established the GHS-R gene knockout mice (GHS-R(-/-)) and found that AMPK activity is notably down-regulated in endothelial cells (ECs) of GHS-R(-/-) mice and the ECs from GHS-R(-/-) mice possess higher proliferative capability than the ECs from wild-type mice. Moreover, AMPK is activated in primary ECs upon Ghrelin induction in vitro. Taking together, the present study unravels that Ghrelin/GHS-R could efficiently activate AMPK in ECs, suggesting a possible mechanism that the roles of Ghrelin/GHS-R in the inhibition of inflammatory response and cell proliferation in AS disease may be partially mediated by activating AMPK.