Circulation, Vol 87, 1715-1721, Copyright © 1993 by American Heart Association
H Ito, M Hiroe, Y Hirata, M Tsujino, S Adachi, M Shichiri, A Koike, A Nogami and F Marumo
BACKGROUND. Cardiac hypertrophy is commonly observed in acromegalic
patients, in whom serum insulin-like growth factor-I (IGF-I) levels are
elevated. In the present study, we examined whether IGF-I induces
hypertrophy in cultured neonatal rat cardiomyocytes through its specific
receptor and whether IGF binding protein-3 (IGFBP-3), which is a major
circulating carrier protein for IGF-I, inhibits IGF-I-induced cardiac
hypertrophy in vitro. METHODS AND RESULTS. Because the response of cardiac
hypertrophy is characterized by the induction of expression for
muscle-specific genes, the effect of IGF-I on steady-state levels of mRNA
for myosin light chain-2 (MLC-2) and troponin I and for skeletal and
cardiac alpha-actin isoforms was evaluated by Northern blot analysis. IGF-I
(10(-7) M) increased mRNA levels for MLC-2 and troponin I as early as 60
minutes with maximum levels by 6 hours, which were maintained for as long
as 24 hours. IGF-I (10(-7) M) also increased transcripts for skeletal
alpha-actin but not for cardiac alpha-actin. The cell size as evaluated
morphometrically was almost doubled after 48-hour treatment with IGF-I.
IGF-I induction of protein synthesis was dose dependent (10(-10) to 10(-7)
M) with a maximal 2.2- fold increase seen at 10(-8) M. In contrast to the
hypertrophic effect of IGF-I, growth hormone affected neither protein
synthesis nor expression for muscle-specific genes. Binding study using
125I-IGF-I revealed the presence of specific binding sites for IGF-I in rat
cardiomyocytes. IGFBP-3 induced a dose-dependent inhibition of protein
synthesis stimulated by IGF-I; IGFBP-3 (10(-7) M) completely inhibited the
[3H]leucine uptake stimulated by IGF-I (10(-8) M). IGFBP-3 similarly
inhibited the IGF-I-stimulated gene expressions for MLC-2 and troponin I.
CONCLUSIONS. These results suggest that IGF-I directly causes cardiac
hypertrophy and that its effect can be blocked by IGFBP- 3.
ARTICLES
Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
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 C. Y. Cheung, D. D. Johnson, and V. Reyes Ontogeny of Insulin-Like Growth Factor-I and -II Gene Expression in Ovine Fetal Heart Reproductive Sciences, November 1, 1996; 3(6): 309 - 315. [Abstract] [PDF]
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Q. Liu, H. Yan, N. J. Dawes, G. A. Mottino, J. S. Frank, and H. Zhu Insulin-like Growth Factor II Induces DNA Synthesis in Fetal Ventricular Myocytes In Vitro Circ. Res., October 1, 1996; 79(4): 716 - 726. [Abstract] [Full Text]
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R. L. Duerr, M. D. McKirnan, R. D. Gim, R. G. Clark, K. R. Chien, and J. Ross Jr Cardiovascular Effects of Insulin-Like Growth Factor-1 and Growth Hormone in Chronic Left Ventricular Failure in the Rat Circulation, June 15, 1996; 93(12): 2188 - 2196. [Abstract] [Full Text]
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J.-S. Zheng, M. O. Boluyt, X. Long, L. O'Neill, E. G. Lakatta, and M. T. Crow Extracellular ATP Inhibits Adrenergic Agonist–Induced Hypertrophy of Neonatal Cardiac Myocytes Circ. Res., April 1, 1996; 78(4): 525 - 535. [Abstract] [Full Text]
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W. Cheng, K. Reiss, P. Li, M. J. Chun, J. Kajstura, G. Olivetti, and P. Anversa Aging Does Not Affect the Activation of the Myocyte Insulin-Like Growth Factor-1 Autocrine System After Infarction and Ventricular Failure in Fischer 344 Rats Circ. Res., April 1, 1996; 78(4): 536 - 546. [Abstract] [Full Text]
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G. Guron, P. Friberg, A. Wickman, C. Brantsing, B. Gabrielsson, and J. Isgaard Cardiac Insulin-like Growth Factor I and Growth Hormone Receptor Expression in Renal Hypertension Hypertension, March 1, 1996; 27(3): 636 - 642. [Abstract] [Full Text]
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A. Cittadini, H. Stromer, S. E. Katz, R. Clark, A. C. Moses, J. P. Morgan, and P. S. Douglas Differential Cardiac Effects of Growth Hormone and Insulin-like Growth Factor1 in the Rat : A Combined In Vivo and In Vitro Evaluation Circulation, February 15, 1996; 93(4): 800 - 809. [Abstract] [Full Text]
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H. Akimoto, H. Ito, M. Tanaka, S. Adachi, M. Hata, M. Lin, H. Fujisaki, F. Marumo, and M. Hiroe Heparin and Heparan Sulfate Block Angiotensin IIInduced Hypertrophy in Cultured Neonatal Rat Cardiomyocytes : A Possible Role of Intrinsic Heparin-like Molecules in Regulation of Cardiomyocyte Hypertrophy Circulation, February 15, 1996; 93(4): 810 - 816. [Abstract] [Full Text]
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J. Gillespie-Brown, S. J. Fuller, M. A. Bogoyevitch, S. Cowley, and P. H. Sugden The Mitogen-activated Protein Kinase Kinase MEK1 Stimulates a Pattern of Gene Expression Typical of the Hypertrophic Phenotype in Rat Ventricular Cardiomyocytes J. Biol. Chem., November 24, 1995; 270(47): 28092 - 28096. [Abstract] [Full Text] [PDF]
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C. Lu, G. Schwartzbauer, M. A. Sperling, S. U. Devaskar, S. Thamotharan, P. D. Robbins, C. F. McTiernan, J.-L. Liu, J. Jiang, S. J. Frank, et al. Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes J. Biol. Chem., June 15, 2001; 276(25): 22892 - 22900. [Abstract] [Full Text] [PDF]
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E. A. Palmieri, G. Benincasa, F. Di Rella, C. Casaburi, M. G. Monti, G. De Simone, L. Chiariotti, L. Palombini, C. B. Bruni, L. Sacca, et al. Differential expression of TNF-alpha , IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H926 - H934. [Abstract] [Full Text] [PDF]
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G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti Increased Cardiac Sympathetic Activity and Insulin-Like Growth Factor-I Formation Are Associated With Physiological Hypertrophy in Athletes Circ. Res., November 23, 2001; 89(11): 977 - 982. [Abstract] [Full Text] [PDF]
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