Xu Mingming, Liu Lin, Song Chenfang, Chen Wei, Gui Shuyan
Department of Geriatric Medicine, Affiliated Nanshan Hospital of Guangdong Medical University, China.
Department of Geriatric Medicine, Affiliated Nanshan Hospital of Guangdong Medical University, China.
Life Sci. 2017 Jun 15;179:23-29. doi: 10.1016/j.lfs.2016.11.025. Epub 2016 Dec 1.
This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy.
VC model was induced by nicotine plus vitamin D in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression.
Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C.
Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC.
本研究旨在探讨胃饥饿素是否通过改善自噬来减轻血管钙化（VC）。
通过尼古丁加维生素D诱导大鼠建立VC模型，并用β-甘油磷酸酯诱导血管平滑肌细胞（VSMC）建立VC模型。采用冯库萨染色或茜素红S染色检测钙沉积情况，同时检测碱性磷酸酶（ALP）活性。采用蛋白质印迹法评估蛋白表达情况。
胃饥饿素治疗可减轻体内和体外VC模型中钙沉积和ALP活性的升高。有趣的是，在VC模型中，胃饥饿素可显著上调自噬标志物LC3和beclin1的蛋白水平。自噬抑制剂3-甲基腺嘌呤可阻断胃饥饿素对VC的改善作用。此外，胃饥饿素处理可使钙化主动脉和VSMC中磷酸化腺苷酸活化蛋白激酶（AMPK）的蛋白表达增加。AMPK抑制剂化合物C可阻止胃饥饿素对自噬诱导和VC减轻的作用。
我们的结果表明，胃饥饿素通过激活AMPK改善自噬，从而减轻VC。这些数据可能为VC的预防和治疗提供线索。
