Mechanical stretch-induced hypertrophy of neonatal rat ventricular myocytes is mediated by β1-integrin-microtubule signaling pathways

Xi Yutao, Geru Wu, Bai Xiaojun, Geng Tao, Ma Aiqun

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background: Mechanical stress plays a crucial role in tissue morphogenesis and remodeling. These processes depend in part on force transmission mediated through integrins and the cytoskeleton. Methods: Ventricular myocytes isolated from neonatal Sprague-Dawley rats (NRVMs) were exposed to persistent centrifugal force stretch for 12 or 24 h. The NRVMs were exposed to colchicine (4 μmol/ml) and anti-integrin β1 specific antibody (10 μg/ml). Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) activity. Incorporation of 3H-leucine, and atrial natriuretic peptide (ANP) and angiotensin II (Ang II) levels were assessed. Pixel intensity and distribution of the microtubule were estimated from laser scanning confocal images. Results: Changes in LDH release and the MTT assay showed that 180 rpm. centrifugal force had minimal effect on the viability and number of NRVMs. Mechanical stretch significantly increased 3H-leucine incorporation into cardiomyocytes. Anti-integrin β1 blocking antibody effectively inhibited the increase in 3H-leucine incorporation and release of ANP (p < 0.05). Following anti-integrin-β1- blocking antibody, the pixel intensity of the microtubule image was decreased after both12 and 24 h stretch, this was similar to the effect of colchicine. Both treatments also inhibited the secretion of Ang II induced by stretch (p < 0.05). Conclusions: Anti-integrin-β1-blocking antibody and colchicine had similar effects, partly inhibiting the stretch-induced increase in microtubule polymerization and the secretion of Ang II in hypertrophic cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)16-22
Number of pages7
JournalEuropean Journal of Heart Failure
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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Keywords

  • β-integrin
  • Cardiomyocyte
  • Hypertrophy
  • Mechanical stretch
  • Microtubule

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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