Cortistatin attenuates vascular calcification in rats.
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.
Liu
Yue
Y
Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Zhou
Ye Bo
YB
Zhang
Gai Gai
GG
Cai
Yan
Y
Duan
Xiao Hui
XH
Teng
Xu
X
Song
Jun Qiu
JQ
Shi
Yi
Y
Tang
Chao Shu
CS
Yin
Xin Hua
XH
Qi
Yong Fen
YF
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
D009479:Neuropeptides; D012333:RNA, Messenger; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; C099323:cortistatin; D000469:Alkaline Phosphatase; D002118:Calcium