Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes.
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 ( approximately 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.
Blaauw
Erik
E
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
van Nieuwenhoven
Frans A
FA
Willemsen
Peter
P
Delhaas
Tammo
T
Prinzen
Frits W
FW
Snoeckx
Luc H
LH
van Bilsen
Marc
M
van der Vusse
Ger J
GJ
D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D049108:Cell Enlargement; D048429:Cell Size; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D007334:Insulin-Like Growth Factor I