title: Cortistatin inhibits calcification of vascular smooth muscle cells by depressing osteoblastic differentiation and endoplasmic reticulum stress.
abstract: Accumulating evidence has indicated that vascular smooth muscular cells (VSMCs) play an important role in the development of vascular calcification (VC). Cortistatin (CST), a novel bio-active peptide, has been shown to exert multiple protective effects on the cardiovascular system. However, the role and possible mechanism of CST in VC remain unclear. Therefore, we used β-glycerophosphoric acid (β-GP) to induce calcification in rat and human VSMCs to determine the effects of CST on osteoblastic differentiation and VSMC mineralization in vitro. Compared with the control, β-GP significantly increased alkaline phosphatase (ALP) activity and calcium content in cultured rat and human VSMCs, as well as multicellular node formation and calcium deposition, as confirmed by von Kossa and Alizarin Red S staining assays. After incubating rat and human VSMCs with β-GP in the presence of different doses of CST (10-8or 10-7mol/L), CST clearly reversed the β-GP-induced increases in ALP activity and calcium content and formation of pathological calcified nodes of VSMCs in a dose-independent manner. Moreover, 10-8and 10-7mol/L CST inhibited the phenotypic transformation of VSMCs into osteoblastic cells by decreasing the osteocalcin protein levels, increasing the SM-α-actin protein levels, and reducing endoplasmic reticulum stress by decreasing the protein expression of glucose-regulated protein 94 and CCAAT/enhancer-binding protein homologous protein. In conclusion, CST directly inhibited β-GP-induced calcification of VSMCs in vitro, probably by suppressing ERS and phenotypic transformation of VSMCs into osteoblastic cells. These results indicate that CST represents a potential target for the prevention and treatment of VC.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China. liuyue198002@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang, China. xinhua_yin@163.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D061205:Vascular Calcification / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
chemical_list: D009479:Neuropeptides; C099323:cortistatin
keywords: Cortistatin; Endoplasmic reticulum stress; Phenotypic transformation; Vascular calcification; Vascular smooth muscular cell