Vascular hypertrophy and hypertension caused by transgenic overexpression of profilin

Moustafa Moustafa-Bayoumi, Mazin A. Alhaj, Osama El-Sayed, Sheik Wisel, Maqsood A. Chotani, Zeinb A. Abouelnaga, Mohamed D.H. Hassona, Katya Rigatto, Mariana Morris, Gerard Nuovo, Jay L. Zweier, Pascal Goldschmidt-Clermont, Hamdy Hassanain

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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.

Original languageEnglish (US)
Pages (from-to)37632-37639
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
StatePublished - Dec 28 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Moustafa-Bayoumi, M., Alhaj, M. A., El-Sayed, O., Wisel, S., Chotani, M. A., Abouelnaga, Z. A., Hassona, M. D. H., Rigatto, K., Morris, M., Nuovo, G., Zweier, J. L., Goldschmidt-Clermont, P., & Hassanain, H. (2007). Vascular hypertrophy and hypertension caused by transgenic overexpression of profilin. Journal of Biological Chemistry, 282(52), 37632-37639. https://doi.org/10.1074/jbc.M703227200