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Mechanical Strain in VSM Cells Triggers Vascular Remodeling and Hypertension and Activates Integrins in Profilin1 Transgenic Model
Author(s) -
abouelnaga zeinb ahmed,
Hassona Mohamed DH,
Awad Mohamed M,
Alhaj Mazin A,
Badary Osama A,
Hamada Farid M,
Bergese Sergio D,
Hassanain Hamdy
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.704.6
Subject(s) - rock2 , focal adhesion , medicine , muscle hypertrophy , rho associated protein kinase , endocrinology , blood pressure , actin , stress fiber , kinase , chemistry , microbiology and biotechnology , biology , phosphorylation
Remodeling is an adaptive process in response to changes in hemodynamic conditions. Increased actin polymerization in VSMCs induces stress fiber formation playing an important role in vascular remodeling via triggering the hypertrophic signaling pathway. We have overexpressed the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increase in F/G‐actin ratio and in the medial thickness of the profilin1 aortas (P<0.05). Western blotting showed significant increase of Phospho‐ERK1/2 and JNK in profilin 1 VSMCs compared to controls (512.3% and 371.4% respectively, P<0.05). A significant increase in ROCK II kinase and Rho‐GTPase activities in aortas of profilin 1 mice (>400%, P<0.05). Our results confirmed the activation of ?PIX and Rac1 which are downstream of focal adhesion kinase (FAK), and the up‐regulation of á7â1 integrins which could be a negative feedback as a result of vascular hypertrophy and hypertension. Monitoring of blood pressure in profilin1 mice 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. Mechanical force is an important modulator of cellular morphology and function and a major contributor to hypertrophy and hypertension.