Faculty Articles

Vascular hypertrophy and hypertension caused by transgenic overexpression of profilin 1.

Publication Title

The Journal of biological chemistry

ISSN

0021-9258

Publication Date

12-1-2007

Keywords

actin polymerization, blood pressure, cDNA overexpression, hypertrophic signaling, jnk activation, erk1/2 phosphorylation, profilin 1, profilin 88r/l mutant, rhodamine-phalloidin staining, rock ii kinase, transgenic fvb/n mice, vascular hypertrophy, vascular smooth muscle cells, western blotting, hypertension, aortic remodeling, cytoskeletal dynamics, signal transduction, vascular physiology, aging-related hypertension

Abstract

We have overexpressed either the cDNA of human profilin 1 or expressed the mutant (88R/L) in the blood vessels of transgenic FVB/N mice. Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin 1 and 88R/L proteins in transgenic mice compared with control (~30%, p < 0.05). Rhodamine-phalloidin staining revealed increase stress fiber formation in vascular smooth muscle cells of profilin 1 compared with 88R/L and control. Hematoxylin and eosin staining showed clear signs of vascular hypertrophy in the aorta of profilin 1 mice versus 88R/L and control. However, there were no differences between 88R/L and control mice. Western blotting confirmed the activation of the hypertrophic signaling cascades in aortas of profilin 1 mice. Phospho-ERK1/2 was significantly higher in profilin 1 than 88R/L and control (512.3 and 361.7%, respectively, p < 0.05). Profilin 1 mice had significant increases in phospho-JNK as compared with 88R/L and control (371.4 and 346%, respectively, p < 0.05). However, there were no differences between 88R/L and control mice in both kinases. There was a significant increase in ROCK II kinase in the aorta of profilin 1 mice compared with controls (>400%, p < 0.05). Tail cuff and circadian monitoring of blood pressure showed significant increases in systolic and mean arterial blood pressures of profilin 1 mice starting at age 6 months compared with controls (~25 mm Hg, p < 0.05). These results suggest that increased actin polymerization in blood vessels triggers activation of the hypertrophic signaling cascades and results in elevation of blood pressure at advanced age.

DOI

10.1074/jbc.M703227200

Volume

282

Issue

52

First Page

37632

Last Page

9

Disciplines

Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy

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