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Int J Clin Exp Pathol 2013;6(9):1770-1780

Original Article
AMPK activity is down-regulated in endothelial cells of GHS-R-/- mice

Min Zhang, Wei-Yi Fang, Xin-Kai Qu, Fang Yuan, Wei-Gang Wang, Jian Fei, Zhi-Gang Wang

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China; School of Life
and Health Sciences, Tongji University, Shanghai 200092, China; Department of General Surgery, the Sixth People’s Hospital, Shanghai
Jiaotong University, Shanghai 200233, China

Received July 16, 2013; Accepted July 26, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: 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. (IJCEP1307029).

Keywords: GHS-R-/-, AMPK, atherosclerosis, ECs, cell proliferation

Address correspondence to: Dr. Zhi-Gang Wang, Department of General Surgery, the Sixth People’s Hospital, Shanghai Jiaotong University,
Shanghai 200233, China. E-mail: wwffzs@126.com