The Role of Integrins in the Regulation of Vascular Hypertrophy in a Profilin 1 Transgenic Mouse Model

Abstract

Increased actin polymerization and stress fiber formation generate mechanical forces that play a role in the modulation of cellular morphology and function. Mechanical stress has a direct effect on the extracellular matrix (ECM) and integrins. To study the effect of stress fiber formation on integrin‐associated activation of hypertrophic signaling in vascular smooth muscle cells (VSMCs), we have overexpressed the human profilin 1 cDNA in vascular smooth muscle cells of FVB/N mice. Western blotting showed a significant increase in á1, â1 and á7 integrin subunits in the aorta of profilin 1 mice compared to control mice (278.9%, 354.7% and 265.7 % respectively, p<0.05). There was significant activation of phospho‐ERK1/2 and phospho‐JNK compared to controls (512% and 371% respectively, p<0.05). In addition, there is a significant increase in â‐pix and Rac 1 (356.4% and 430.6% respectively, p < 0.05). Our results additionally demonstrated an increase in superoxide production in the aortas of profilin1 mice (400%, p<0.05). In conclusion, increased stress fiber formation in VSMCs activates á1, â1 and á7 integrins that trigger the activation of hypertrophic signaling and modulate changes in oxidative stress.