Résumé
Objective Integrins contribute to vascular morphogenesis through regulation of adhesion and assembly of the extracellular matrix. However, the role of 1-integrin in the mature vascular wall is less clear.
Approach and Results We sought to determine the function of 1-integrin in mature smooth muscle cells in vivo using a loss of function approach by crossing a tamoxifen-inducible sm22Cre line to a floxed 1-integrin transgenic line. Adult mice lacking smooth muscle 1-integrin survived only 10 weeks post induction. The deletion of 1-integrin resulted in profound loss of vasomotor control. Histological analysis revealed progressive fibrosis in arteries with associated apoptosis of smooth muscle cells, which was not rescued by adventitial stem cells. Smooth muscle cell apoptosis was detected in arteries with dead cells replaced primarily by collagen. Despite the catastrophic effects on vascular smooth muscle, the deleted visceral smooth muscle remained viable with the exception of a short portion of the colon, indicating that vascular but not visceral smooth muscle is particularly sensitive to changes in 1-integrin.
Conclusions This study reveals an essential function of 1-integrin in the maintenance of vasomotor control and highlights a critical role for 1-integrin in vascular, but not visceral, smooth muscle survival.