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MFAP4 is an integrin αVβ3/5 ligand involved in vascular remodeling

ABSTRACT: Arterial injury or occlusive arterial disease may stimulate healing responses, which when overexuberant, leads to restenosis of the injured vessel. This response is influenced by specific integrin signalling in vascular smooth muscle cells (VSMCs). Microfibril-associated protein 4 (MFAP4) colocates in blood vessels with elastic fibers. MFAP4 contains an N-terminal RGD-motiv, which is a potential integrin binding site. The role for MFAP4 in vascularproliferative disease is so far unknown and the subject for these investigations. Here we show that MFAP4 is expressed and secreted by VSMCs and binds elastin and collagen. MFAP4 mediated adhesion, and migration, and proliferation of VSMCs in an integrin αVβ3/5 dependent manner and the effects were inhibited by MFAP4 blocking antibodies. MFAP4 deficient mutant mice were generated and appeared with a normal cardiophysiological phenotype. When challenged by carotid artery ligation, the MFAP4 deficient mice had delayed neointimal formation and the compensatory outward remodeling of the vessel diameter and thus the vessel lumen was reduced. MFAP4 expression appeared unaffected by the induced pathology. HUMANE DATA This new MFAP4 mediated molecular mechanism for regulation of integrin αVβ3/5 signalling may have therapeutic implications in diseases where VSMC migration and proliferation are involved in the pathogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE40480 | GEO | 2013/04/01

SECONDARY ACCESSION(S): PRJNA174320

REPOSITORIES: GEO

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