Role of transforming growth factor-β in maintenance of function of cultured neonatal cardiac myocytes : autocrine action and reversal of damaging effects of interleukin-1

The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta 1 has also been localized intracellularly to both mitochondria and contractile...

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Bibliographic Details
Published in:The Journal of clinical investigation 1992-11, Vol.90 (5), p.2056-2062
Main Authors: ROBERTS, A B, ROCHE, N. S, WINOKUR, T. S, BURMESTER, J. K, SPORN, M. B
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn - physiology
Biological and medical sciences
cardiac muscle
Cardiology. Vascular system
Cells, Cultured
Heart
Heart - drug effects
Heart Rate - drug effects
injuries
interleukin 1
Interleukin-1 - toxicity
mediation
Medical sciences
Myocardial Contraction - drug effects
Myocarditis. Cardiomyopathies
myocardium
protection
Rats
Transforming Growth Factor beta - pharmacology
transforming growth factor- beta
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Summary:The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta 1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-beta stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-beta, we show that endogenous TGF-beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1 beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-beta can overcome this inhibition. The antagonistic effects of TGF-beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci116087