Back to Search
Start Over
Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice
- Source :
- The Tohoku journal of experimental medicine. 221(4)
- Publication Year :
- 2010
-
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.
- Subjects :
- Vitamin
Male
medicine.medical_specialty
Bone Morphogenetic Protein 7
Osteocalcin
chemistry.chemical_element
Aorta, Thoracic
Calcium
General Biochemistry, Genetics and Molecular Biology
Muscle, Smooth, Vascular
chemistry.chemical_compound
Mice
Internal medicine
medicine
Vitamin D and neurology
Animals
Humans
Osteopontin
Cells, Cultured
Cholecalciferol
Osteoblasts
biology
Dose-Response Relationship, Drug
Myocardium
Calcinosis
Heart
General Medicine
Recombinant Proteins
Blot
Bone morphogenetic protein 7
Mice, Inbred C57BL
Dose–response relationship
Drug Combinations
Endocrinology
chemistry
Glycerophosphates
biology.protein
Drug Antagonism
Subjects
Details
- ISSN :
- 13493329
- Volume :
- 221
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Tohoku journal of experimental medicine
- Accession number :
- edsair.doi.dedup.....f7852376ae5e062abdd9f85beafaf51f