title: Angiotensin-(1-7) inhibits vascular calcification in rats.
abstract: Angiotensin-(1-7) [Ang-(1-7)] is a new bioactive heptapeptide in the renin-angiotensin-aldosterone system (RAAS) with potent protective effects in cardiovascular diseases, opposing many actions of angiotensin II (Ang II) mediated by Ang II type 1 (AT1) receptor. It is produced mainly by the activity of angiotensin-converting enzyme 2 (ACE2) and acts through the Mas receptor. However, the role of Ang-(1-7) in vascular calcification (VC) is still unclear. In this study, we investigated the protective effects of Ang-(1-7) on VC in an in vivo rat VC model induced by vitamin D3 plus nicotine. The levels of ACE2 and the Mas receptor, as well as ACE, AT1 receptor, Ang II type 2 receptor and angiotensinogen, were significantly increased in calcified aortas, and Ang-(1-7) reversed the increased levels. Ang-(1-7) restored the reduced expression of lineage markers, including smooth muscle (SM) α-actin, SM22α, calponin and smoothelin, in vascular smooth muscle cells (VSMCs) and retarded the osteogenic transition of VSMCs by decreasing the expression of bone-associated proteins. It reduced alkaline phosphatase activity and calcium deposition in VC and alleviated the hemodynamic disorders of rats with VC. We provide the first in vivo evidence that Ang-(1-7) can inhibit the development of VC by inhibiting the osteogenic transition of VSMCs, at least in part by decreasing levels of the ACE/Ang II/AT1 axis. The increased expression of ACE2 and the Mas receptor in calcified aortas suggests the involvement of the ACE2/Ang-(1-7)/Mas axis during VC. Ang-(1-7) might be an efficient endogenous vasoprotective factor for VC.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China.
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Sui
authors.forename: Jin-Rui
authors.initials: JR
authors.lastname: Chang
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Zhang
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Yu
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: D000199:Actins / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D002762:Cholecalciferol / Q000009:adverse effects; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D061205:Vascular Calcification / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000096985:Calponins
chemical_list: D000199:Actins; D000469:Alkaline Phosphatase; D000803:Angiotensin I; D000804:Angiotensin II; D000085962:Angiotensin-Converting Enzyme 2; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002762:Cholecalciferol; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009538:Nicotine; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000096985:Calponins; C491051:Smtn protein, rat; C000705329:Ace2 protein, rat; C118790:angiotensin I (1-7)