Matrix Gla protein reinforces angiogenic resolution.

Abstract:

:Matrix Gla Protein (MGP) is an ECM molecule commonly associated with dysfunctions of large blood vessels such as arteriosclerosis and atherosclerosis. However, the exact role of MGP in the microvasculature is not clear. Utilizing a mouse MGP knockout model we found that MGP suppresses angiogenic sprouting from mouse aorta restricts microvascular density in cardiac and skeletal muscle, and is an endogenous inhibitor of tumor angiogenesis. Similarly, morpholino based knockdown of MGP in zebrafish embryos caused a progressive loss of luminal structures in intersegmental vessels, a phenotype reminiscent of Dll4/Notch inhibition. Accordingly, MGP suppressed Notch-dependent Hes-1 promoter activity and expression of Jagged1 mRNA relative to Dll4 mRNA. However, inhibition of BMP but not Notch or VEGF signaling reversed the excessive angiogenic sprouting phenotype of MGP knockout aortic rings suggesting that MGP may normally suppress angiogenic sprouting by blocking BMP signaling. Collectively, these results suggest that MGP is a multi-functional inhibitor of normal and abnormal angiogenesis that may function by coordinating with both Notch and BMP signaling pathways.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Sharma B,Albig AR

doi

10.1016/j.mvr.2012.10.005

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

24-33

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(12)00168-9

journal_volume

85

pub_type

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