Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes

Erik Blaauw, Frans A. van Nieuwenhoven, Peter Willemsen, Tammo Delhaas, Frits W. Prinzen, Luc H. Snoeckx, Marc van Bilsen, Ger J. van der Vusse*

*Corresponding author for this work

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Abstract

Blaauw E, van Nieuwenhoven FA, Willemsen P, Delhaas T, Prinzen FW, Snoeckx LH, van Bilsen M, van der Vusse GJ. Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes. Am J Physiol Heart Circ Physiol 299: H780-H787, 2010. First published July 16, 2010; doi:10.1152/ajpheart.00822.2009.-Both mechanical and humoral triggers have been put forward to explain the hypertrophic response of the challenged cardiomyocyte. The aim of the present study was to investigate whether cyclic equibiaxial stretch is a direct stimulus for isolated adult rabbit cardiomyocytes to develop hypertrophy and to explore the potential involvement of the autocrine/paracrine factors ANG II, transforming growth factor (TGF)-beta(1), and IGF-I in this process. Isolated cardiomyocytes were exposed to 10% cyclic equibiaxial stretch (1 Hz) for up to 48 h or treated with ANG II (100 nM), TGF-beta(1) (5 ng/ml), IGF-I (100 ng/ml), ANG II type 1 (AT(1)) receptor blockers, or conditioned medium of stretched fibroblasts. Cyclic stretch significantly increased cell surface area (+3.1%), protein synthesis (+21%), and brain natriuretic peptide (BNP) mRNA expression (6-fold) in cardiomyocytes. TGF-beta(1) expression increased (+42%) transiently at 4 h, whereas cardiomyocyte IGF-I expression was not detectable under all experimental conditions. The AT(1) receptor blockers candesartan and irbesartan (100 nM) did not prevent the stretch-induced hypertrophic response. Direct exposure to ANG II, TGF-beta(1), or IGF-I did not enhance cardiomyocyte BNP expression. In cardiac fibroblasts, stretch elicited a significant approximately twofold increase in TGF-beta(1) and IGF-I expression. Conditioned medium of stretched fibroblasts increased BNP expression in cardiomyocytes (similar to 2-fold, P = 0.07). This study clearly indicates that cyclic stretch is a strong, direct trigger to induce hypertrophy in fully differentiated rabbit cardiomyocytes. The present findings do not support the notion that stretch-mediated hypertrophy of adult rabbit cardiomyocytes involves autocrine/paracrine actions of ANG II, TGF-beta(1), or IGF-I.
Original languageEnglish
Pages (from-to)H780-H787
JournalAmerican Journal of Physiology-heart and Circulatory Physiology
Volume299
Issue number3
DOIs
Publication statusPublished - Sep 2010

Keywords

  • fibroblasts
  • transforming growth factor-beta(1)
  • angiotensin II
  • insulin-like growth factor-I
  • brain natriuretic peptide

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