title: Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice.
abstract: Vascular calcification refers to the deposition of calcium phosphate in cardiovascular tissues, including arteries and myocardium. Vascular calcification is frequently associated with cardiovascular disease. Recently, bone morphgenetic protein-7 (BMP-7) has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been fully elucidated. We therefore tested the hypothesis that BMP-7 inhibits vascular calcification by using two conditions, high levels of vitamin D and phosphate, each of which could enhance vascular calcification. C57BL/6 mice were treated for 3 days with high vitamin D (500,000 IU/kg/day) in the presence or absence of recombinant human BMP-7 (rhBMP-7). Expression levels of osteopontin and osteocalcin, markers of the osteoblastic phenotype, were assessed by immunohistochemical staining or Western blotting analysis. Vitamin D increased calcium staining in thoracic aortas and hearts and the expression levels of osteopontin and osteocalcin in mice. Importantly, pretreatment for 7 days and subsequent treatment for 3 days with rhBMP-7 (10 microg/kg/day) abolished the vitamin D-mediated increases in the above parameters. In addition, human aortic smooth muscle cells (HASMCs) were cultured with high beta-glycerophosphate, a phosphate donor, for 2 weeks in the presence or absence of rhBMP-7. High beta-glycerophosphate increased expression levels of osteopontin and osteocalcin as well as calcium staining in HASMCs, but these changes were attenuated by treatment with BMP-7. Thus, BMP-7 inhibits vascular calcification associated with high levels of vitamin D or phosphate. We propose that BMP-7 treatment may be helpful in reducing the risks of cardiovascular disease related to vascular calcification.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Yang Ho
authors.initials: YH
authors.lastname: Kang
authors.forename: Jung Sook
authors.initials: JS
authors.lastname: Jin
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Yi
authors.forename: Seok Man
authors.initials: SM
authors.lastname: Son
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D002114:Calcinosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D005994:Glycerophosphates / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D055419:Bone Morphogenetic Protein 7; D004338:Drug Combinations; D005994:Glycerophosphates; D011994:Recombinant Proteins; D015675:Osteocalcin; D053495:Osteopontin; D002762:Cholecalciferol; C031463:beta-glycerophosphoric acid