Intermedin1-53 attenuates aging-associated vascular calcification in rats by upregulating sirtuin 1.
Vascular calcification is a common phenomenon in older adults. Intermedin (IMD) is a cardiovascular bioactive peptide inhibiting vascular calcification. In this study, we aimed to investigate whether IMD1-53 attenuates aging-associated vascular calcification. Vascular calcification was induced by vitamin D3 plus nicotine (VDN) in young and old rats. The calcification in aortas was more severe in old rats treated with VDN than young control rats, and IMD expression was lower. Exogenous administration of IMD1-53 significantly inhibited the calcium deposition in aortas and the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) in VDN-treated old rats. Moreover, levels of aging-related p16, p21 and β-galactosidase were all greatly decreased by IMD1-53. These results were further confirmed in rat and human VSMCs in vitro. In addition, IMD-deficient mouse VSMCs showed senescence features coinciding with osteogenic transition as compared with wild-type mouse VSMCs. Mechanistically, IMD1-53 significantly increased the expression of the anti-aging factor sirtuin 1 (sirt1); the inhibitory effects of IMD1-53 on calcification and senescence were blocked by sirt1 knockdown. Furthermore, preincubation with inhibitors of PI3K, AMPK or PKA efficiently blunted the upregulatory effect of IMD1-53 on sirt1. Consequently, IMD1-53 could attenuate aging-associated vascular calcification by upregulating sirt1 via activating PI3K/Akt, AMPK and cAMP/PKA signaling.
['Chen|Yao|Y|', 'Zhang|Lin-Shuang|LS|', 'Ren|Jin-Ling|JL|', 'Zhang|Ya-Rong|YR|', 'Wu|Ning|N|', 'Jia|Mo-Zhi|MZ|', 'Yu|Yan-Rong|YR|', 'Ning|Zhong-Ping|ZP|', 'Tang|Chao-Shu|CS|', 'Qi|Yong-Fen|YF|']
D000375:Aging D000818:Animals D001011:Aorta D054338:Cell Transdifferentiation D002762:Cholecalciferol D004195:Disease Models, Animal D008297:Male D051379:Mice D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D009538:Nicotine D010012:Osteogenesis D036361:Peptide Hormones D051381:Rats D017207:Rats, Sprague-Dawley D056564:Sirtuin 1 D015854:Up-Regulation D061205:Vascular Calcification
vascular calcification intermedin vascular smooth muscle cell sirt1 aging