title: Cortistatin attenuates vascular calcification in rats.
abstract: Cortistatin (CST) is a newly discovered polypeptide with multiple biological activities that plays a regulatory role in the nervous, endocrine and immune systems. However, the role of CST in the pathogenesis of cardiovascular diseases remains unclear. In this study, we investigated in rats whether CST inhibits vascular calcification induced by vitamin D3 and nicotine treatment in vivo and calcification of cultured rat vascular smooth muscular cells (VSMCs) induced by beta-glycerophosphate in vitro and the underlying mechanism. We measured rat hemodynamic variables, alkaline phosphatase (ALP) activity, calcium deposition and pathological changes in aortic tissues and cultured VSMCs. CST treatment significantly improved hemodynamic values and arterial compliance in rats with vascular calcification, by decreasing systolic blood pressure, pulse pressure, left ventricular end-systolic pressure and left ventricular end-diastolic pressure. CST also significantly decreased ALP activity and calcium deposition, alleviated pathological injury and down-regulated the mRNA expression of type III sodium-dependent phosphate co-transporter-1 (Pit-1) in aortic tissues. It dose-independently inhibited the calcification of VSMCs by decreasing ALP activity and calcium deposition, alleviating pathologic injury and down-regulating Pit-1 mRNA expression. As with CST treatment, ALP activation and calcium deposition were decreased significantly on treatment with ghrelin, the endogenous agonist of growth hormone secretagogue receptor 1a (GHSR1a), but not significantly with somatostatin-14 or proadrenomedullin N-terminal 20 peptide in VSMCs. Further, growth hormone-releasing peptide-6[D-lys], the endogenous antagonist of GHSR1a, markedly reversed the increased ALP activity and calcium deposition in VSMCs. CST could be a new target molecule for the prevention and therapy of vascular calcification, whose effects are mediated by GHSR1a rather than SSTRs or Mrg X2.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Ye Bo
authors.initials: YB
authors.lastname: Zhou
authors.forename: Gai Gai
authors.initials: GG
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Duan
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.forename: Jun Qiu
authors.initials: JQ
authors.lastname: Song
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Chao Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Yin
authors.forename: Yong Fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000009:adverse effects* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; C099323:cortistatin; D000469:Alkaline Phosphatase; D002118:Calcium