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An essential requirement for ?1 integrin in the assembly of extracellular matrix proteins within the vascular wall.

ABSTRACT: ?1 integrin has been shown to contribute to vascular smooth muscle cell differentiation, adhesion and mechanosensation in vitro. Here we showed that deletion of ?1 integrin at the onset of smooth muscle differentiation resulted in interrupted aortic arch, aneurysms and failure to assemble extracellular matrix proteins. These defects result in lethality prior to birth. Our data indicates that ?1 integrin is not required for the acquisition, but it is essential for the maintenance of the smooth muscle cell phenotype, as levels of critical smooth muscle proteins are gradually reduced in mutant mice. Furthermore, while deposition of extracellular matrix was not affected, its structure was disrupted. Interestingly, defects in extracellular matrix and vascular wall assembly, were restricted to the aortic arch and its branches, compromising the brachiocephalic and carotid arteries and to the exclusion of the descending aorta. Additional analysis of ?1 integrin in the pharyngeal arch smooth muscle progenitors was performed using wnt1Cre. Neural crest cells deleted for ?1 integrin were able to migrate to the pharyngeal arches and associate with endothelial lined arteries; but exhibited vascular remodeling defects and early lethality. This work demonstrates that ?1 integrin is dispensable for migration and initiation of the smooth muscle differentiation program, however, it is essential for remodeling of the pharyngeal arch arteries and for the assembly of the vessel wall of their derivatives. It further establishes a critical role of ?1 integrin in the protection against aneurysms that is particularly confined to the ascending aorta and its branches.

SUBMITTER: Turlo KA

PROVIDER: S-EPMC3590017 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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An essential requirement for β1 integrin in the assembly of extracellular matrix proteins within the vascular wall.

Turlo Kirsten A KA Noel Onika D V OD Vora Roshni R LaRussa Marie M Fassler Reinhard R Hall-Glenn Faith F Iruela-Arispe M Luisa ML

Developmental biology 20120210 1

β1 integrin has been shown to contribute to vascular smooth muscle cell differentiation, adhesion and mechanosensation in vitro. Here we showed that deletion of β1 integrin at the onset of smooth muscle differentiation resulted in interrupted aortic arch, aneurysms and failure to assemble extracellular matrix proteins. These defects result in lethality prior to birth. Our data indicates that β1 integrin is not required for the acquisition, but it is essential for the maintenance of the smooth mu ...[more]

PMID: 22331032

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An essential requirement for ?1 integrin in the assembly of extracellular matrix proteins within the vascular wall.

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An essential requirement for β1 integrin in the assembly of extracellular matrix proteins within the vascular wall.

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