Abstract
Recently it has become appreciated that the myocardium produces several growth factors (cytokines) and that their expression is highly regulated not only in development but also in injury and disease [1]. One of these cytokines, transforming growth factor-ß (TGF-ß), a dimeric, multifunctional peptide [2], is expressed at high levels in the heart during both embryonic and adult life [3,4]. In this brief review, we will discuss the results of investigations directed at elucidating the role of TGF-ß in the heart with emphasis on its localization in the adult myocardium, its possible function in maintaining the rhythmic, contractile nature of cardiac tissue, and its role in response of the heart to injury and to ischemia.
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References
Schneider MD, Parker TD. Cardiac growth factors. Rec Prog Growth Factor Res 1991; 3:1–26.
Roberts AB, Sporn MB. The transforming growth factors-ß, In: Sporn MB, Roberts AB editors: Handbook of Experimental Pharmacology. Peptide Growth Factors and Their Receptors. Springer-Verlag, Berlin, 1990; 95: 419–472.
Thompson NL, Bazoberry F, Speir EH, et al. Transforming growth factor-ßl in acute myocardial infarction in rats. Growth Factors 1988; 1: 91–99.
Thompson NL, Flanders KC, Smith JM, et al. Expression of transforming growth factor-ßl in specific cells and tissues of adult and neonatal mice. J Cell Biol 1989; 108: 661–669.
Roberts AB, Anzano MA, Lamb LC, et al. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci U S A 1981; 78: 5339–5343.
Heine UI, Burmester JK, Flanders KC, et al. Localization of transforming growth factor-ßl in mitochondria of murine heart and liver. Cell Regulation 1991; 2: 467–477.
Dahlback B, Hildebrand B, Linse S. Novel type of very high affinity calcium-binding sites in ß-hydroxy-asparagine-containing epidermal growth factor-like domains in vitamin K-dependent proteins. J Biol Chem 1990; 265: 18481–18489.
Kansaki T, Olofsson A, Moren A, et al. TGF-ßl binding protein: a component of the large latent complex of TGF-ßl with multiple repeat sequences. Cell 1990; 61: 1051–1061.
Qian SW, Kondaiah P, Casscells W, et al. A second messenger RNA species of transforming growth factor-ßl in infarcted rat heart. Cell Regulation 1991; 2: 241–249.
Kim S-J, Kim K-Y, Wakefield LM, et al: Post-transcriptional regulation of the human transforming growth factor-ßl gene. J Biol Chem 1992; 267: 13702–13707.
Lefer AM, Tsao P, Aoki N, et al. Mediation of cardioprotection by transforming growth factor-ß. Science 1990; 249: 61–64.
Lefer AM. Mechanisms of the protective effects of transforming growth factor-ß in reperfusion injury. Biochem Pharmacol 1991 42: 1323–1327.
Gamble JR, Vadas MA. Endothelial adhesiveness for blood neutrophils is inhibited by transforming growth factor-ß. Science 1988; 242: 97–99.
Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-ß (TGF-ß). Growth Factors 1992; in press.
Roberts AB, Roche NS, Winokur TS, et al. Role of TGF-ß in maintenance of function of cultured cardiac myocytes: autocrine action and reversal of damaging effects of interleukin-1. J Clin Invest 1992; in press.
Gulick T, Chung MK, Pieper SJ, et al. Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte ß-adrenergic responsiveness. Proc Natl Acad Sci U S A 1989; 86: 6753–6757.
Heino J, Heinonen T. Interleukin-1 ß prevents the stimulatory effect of transforming growth factor-ß on collagen gene expression in human skin fibroblasts. Biochem J 1990; 271: 827–830.
Musso T, Espinoza-Delgado I, Pulkki K, et al. Transforming growth factor ß downregulates interleukin-1 (IL-l)-induced IL-6 production by human monocytes. Blood 1990; 76: 2466–2469.
Pfeilschifter J, Pignat W, Leighton J, et al. Transforming growth factor ß2 differentially modulates interleukin-1 ß and tumour-necrosis-factor-α-stimulated phospholipase A2 and prostaglandin E2 synthesis in rat renal mesangial cells. Biochem J 1990; 270: 269–271.
Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992; 6: 3051–3064.
Finkel MS, Oddis CV, Jacob TD, et al. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992; 257: 387–389.
Matheis G, Sherman MP, Buckberg GD, et al. Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am J Physiol 1992; 262: H616–H620.
Schulz R, Nava E, Moncada S. Induction and potential biological relevance of a Ca2+-independent nitric oxide synthase in the myocardium. Br J Pharmacol 1992; 105: 575–580.
Roberts AB, Vodovotz Y, Roche NS, et al. Role of nitric oxide in antagonistic effects of TGF-ß and IL-lß on the beating rate of cultured cardiac myocytes. Molec Endocrinol 1992; in press.
Ignarro JJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 1990; 30: 535–560.
Roberts AB, Sporn MB. Mechanistic interrelationships between two superfamilies: the steroid/retinoid receptors and transforming growth factor-ß. Cancer Surveys 1992; 14: 205–220.
Kilbourn RG, Griffith OW. Overproduction of nitric oxide in cytokine-mediated and septic shock. J Natl Cancer Inst 1992; 84: 827–831.
Furukawa K-I, Ohshima N, Tawada-Iwata Y, et al. Cyclic GMP stimulates Na+/Ca2+ exchange in vascular smooth muscle cells in primary culture. J Biol Chem 1991; 266: 12337–12341.
Méry PF, Lohmann SM, Walter U, et al: Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci U S A 1991; 88: 1197–1201.
Stamler JS, Simon DI, Osborne JA, et al. S-Nitrosylation of proteins with nitric oxide: Synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A 1992; 89: 444–48.
Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 1989; 13: 1637–1652
Vukicevic S, Kleinman H, Luyten FP, et al. Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp Cell Res 1992; in press.
Eddy LJ, Goeddel DV, Wong GHW. Tumor necrosis factor-α pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 1992; 184: 1056–1059.
Brown JM, Grosso MA, Terada LS, et al. Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts Proc Natl Acad Sci USA 1989; 86: 2516–2520.
Brown JM, White CW, Terada LS, et al. Interleukin-1 pretreatment decreases ischemia/reperfusion injury. Proc Natl Acad Sci USA 1990; 87: 5026–5030.
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Roberts, A.B., Sporn, M.B. (1993). Transforming growth factor-ß: localization and possible functional roles in cardiac myocytes. In: Cummins, P. (eds) Growth Factors and the Cardiovascular System. Developments in Cardiovascular Medicine, vol 147. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3098-5_4
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DOI: https://doi.org/10.1007/978-1-4615-3098-5_4
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