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

First Author  Turlo KA Year  2012
Journal  Dev Biol Volume  365
Issue  1 Pages  23-35
PubMed ID  22331032 Mgi Jnum  J:184940
Mgi Id  MGI:5426759 Doi  10.1016/j.ydbio.2012.01.027
Citation  Turlo KA, et al. (2012) An essential requirement for beta1 integrin in the assembly of extracellular matrix proteins within the vascular wall. Dev Biol 365(1):23-35
abstractText  beta1 integrin has been shown to contribute to vascular smooth muscle cell differentiation, adhesion and mechanosensation in vitro. Here we showed that deletion of beta1 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 beta1 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 beta1 integrin in the pharyngeal arch smooth muscle progenitors was performed using wnt1Cre. Neural crest cells deleted for beta1 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 beta1 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 beta1 integrin in the protection against aneurysms that is particularly confined to the ascending aorta and its branches.
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