Abstract | RATIONALE: OBJECTIVE: 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.
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Authors | Yucheng Yao, Brian J Bennett, Xuping Wang, Michael E Rosenfeld, Cecilia Giachelli, Aldons J Lusis, Kristina I Boström |
Journal | Circulation research
(Circ Res)
Vol. 107
Issue 4
Pg. 485-94
(Aug 20 2010)
ISSN: 1524-4571 [Electronic] United States |
PMID | 20576934
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins E
- Bone Morphogenetic Proteins
- Calcium-Binding Proteins
- Extracellular Matrix Proteins
- matrix Gla protein
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Topics |
- 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)
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