Biomechanical Stress in VSM Cells Leads to Vascular Remodeling and Hypertension in Profilin 1 Transgenic Mouse Model

Abstract

Actin polymerization is dynamically regulated and is essential for vascular smooth muscle contraction. Profilin 1 promotes actin assembly from G‐actin into F‐actin. We overexpressed the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increase in F/G‐actin ratio in VSMCs in profilin 1 mice (301 ± 4%) compared to controls (153 ± 5%; P<0.0001) and increase in the medial thickness (138 ±4 μm) compared to control (90 ±3 μm; P<0.05). Western blotting confirmed the activation of the hypertrophic signaling in the aortas of profilin 1 mice. Phospho‐ERK1/2 was significantly higher in profilin 1 than control (512.3% and 361.7%, P<0.05). Profilin 1 mice had significant increase in phospho‐JNK compared to control (371.4% and 346%, P<0.05). There was a significant increase in ROCK II kinase in aorta of profilin 1 mice compared to control (>400%, P<0.05). RT‐PCR analysis confirmed the activation of Rac 1, eNOS and significant changes in antioxidant signaling. Monitoring of blood pressure showed significant increase in systolic and mean arterial blood pressure of profilin 1 mice starting at age 6 month (~ 25 mmHg, P<0.05). Isometeric tension analysis in mesenteric arteries showed significant differences in response to vasoactive drugs. These results suggest the regulation of blood pressure is directly related to F/G actin ratio in VSMCs. Startup fund.