Document Detail


Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification.
MedLine Citation:
PMID:  20576934     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The bone morphogenetic proteins (BMPs), a family of morphogens, have been implicated as mediators of calcification and inflammation in the vascular wall.
OBJECTIVE: To investigate the effect of altered expression of matrix Gla protein (MGP), an inhibitor of BMP, on vascular disease.
METHODS AND RESULTS: We used MGP transgenic or MGP-deficient mice bred to apolipoprotein E mice, a model of atherosclerosis. MGP overexpression reduced vascular BMP activity, atherosclerotic lesion size, intimal and medial calcification, and inflammation. It also reduced expression of the activin-like kinase receptor 1 and the vascular endothelial growth factor, part of a BMP-activated pathway that regulates angiogenesis and may enhance lesion formation and calcification. Conversely, MGP deficiency increased BMP activity, which may explain the diffuse calcification of vascular medial cells in MGP deficient aortas and the increase in expression of activin-like kinase receptor 1 and vascular endothelial growth factor. Unexpectedly, atherosclerotic lesion formation was decreased in MGP-deficient mice, which may be explained by a dramatic reduction in expression of endothelial adhesion molecules limiting monocyte infiltration of the artery wall.
CONCLUSIONS: Our results indicate that BMP signaling is a key regulator of vascular disease, requiring careful control to maintain normal vascular homeostasis.
Authors:
Yucheng Yao; Brian J Bennett; Xuping Wang; Michael E Rosenfeld; Cecilia Giachelli; Aldons J Lusis; Kristina I Boström
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-24
Journal Detail:
Title:  Circulation research     Volume:  107     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-09-16     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  485-94     Citation Subset:  IM    
Affiliation:
Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1679, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins E / deficiency
Atherosclerosis / metabolism,  prevention & control*
Bone Morphogenetic Proteins / antagonists & inhibitors*,  biosynthesis
Calcinosis / metabolism,  prevention & control*
Calcium-Binding Proteins / biosynthesis
Extracellular Matrix Proteins / biosynthesis
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Vascular Diseases / metabolism,  prevention & control*
Grant Support
ID/Acronym/Agency:
HL30568/HL/NHLBI NIH HHS; HL81397/HL/NHLBI NIH HHS; P01 HL030568-250010/HL/NHLBI NIH HHS; P01 HL030568-26A18180/HL/NHLBI NIH HHS; R01 HL081397-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Bone Morphogenetic Proteins; 0/Calcium-Binding Proteins; 0/Extracellular Matrix Proteins; 0/matrix Gla protein
Comments/Corrections

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