Regulation of Smooth Muscle Cell Phenotype by the Alpha7beta1 Integrin

To examine the function of the alpha7beta1 integrin in vascular development and integrity, we have created alpha7 integrin null mice using a LacZ knockin strategy. The LacZ gene was used to identify the expression pattern of the alpha7 integrin during development. alpha7 integrin expression was detected in the central and peripheral nervous system and vasculature. Loss of the alpha7 integrin chain results in partial embryonic lethality. Analysis of embryos revealed cerebral vascular hemorrhaging starting at embryonic day (ED) 10.5 and reduced cerebral vascularization. In addition, surviving alpha7 integrin null mice displayed vascular defects, including vascular smooth muscle cell hyperplasia and hypertrophy. Altered alpha5 and alpha6B integrin expression in the vasculature may also contribute to the vascular pathology observed in alpha7 integrin null mice. Together, these results suggest a role for the alpha7beta1 integrin in the progression of cardiovascular disease.