Relative cardiac expression of growth hormone receptor and insulin-like growth factor-I mRNA in congenital heart disease
- 35 Downloads
- 4 Citations
Abstract
GH may exert direct growth-promoting and metabolic actions on target tissues, but most of its effects are mediated by circulating (endocrine) or local (auto-/paracrine) IGF-I. The GH/IGF-I system has an important role in cardiac development and in maintaining the structure and function of the heart. A subgroup of children with pronounced heart defects will eventually need transplants, owing to congestive heart failure. Since the symptoms are often severe and may progress while waiting for surgery, it is necessary to develop supportive medical treatment. GH has been proposed as a therapeutic agent in adults with heart failure, but to date studies are lacking on children and more information is necessary. We have examined the expression of IGF-I mRNA and GH-receptor (GH-R) mRNA in children undergoing surgery for congenital heart disease. Eighteen children scheduled for open-heart surgery were included in the study. Right auricular biopsies were taken at the time of venous catheterization preceding cardiac bypass. The specimens were analysed using realtime PCR. We were able to show expression of both IGF-I mRNA and GH-R mRNA in the pediatric heart. The relative expressions were inter-correlated (r=0.75, p<0.001). GH-R mRNA correlated positively to standardized weight (r=0.65, p=0.004), body mass index (BMI) (r=0.59, p=0.01), and standardized BMI (r=0.59, p=0.01). IGF-I mRNA only correlated to BMI (r=0.50, p=0.04). This is the first study displaying cardiac expression of IGF-I mRNA and GH-R mRNA in children with congenital heart disease, although further studies are needed to define a role for GH in the treatment of these patients.
Key-words
Growth hormone insulin-like growth factor-I congenital heart disease children cardiac surgeryPreview
Unable to display preview. Download preview PDF.
References
- 1.Svensson J, Tivesten A, Isgaard J. Growth hormone and the cardiovascular function. Minerva Endocrinol 2005, 30: 1–3.PubMedGoogle Scholar
- 2.Sjögren K, Liu JL, Blad K, et al. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci U S A 1999, 96: 7088–92.PubMedCentralPubMedCrossRefGoogle Scholar
- 3.Mathews LS, Enberg B, Norstedt G. Regulation of rat growth hormone receptor gene expression. J Biol Chem 1989, 264: 9905–10.PubMedGoogle Scholar
- 4.Isgaard J, Nilsson A, Vikman K, Isaksson OG. Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle. J Endocrinol 1989, 120: 107–12.PubMedCrossRefGoogle Scholar
- 5.Toyozaki T, Hiroe M, Hasumi M, et al. Insulin-like growth factor I receptors in human cardiac myocytes and their relation to myocardial hypertrophy. Jpn Circ J 1993, 57: 1120–7.PubMedCrossRefGoogle Scholar
- 6.Barton PJ, Felkin LE, Birks EJ, et al. Myocardial insulin-like growth factor-I gene expression during recovery from heart failure after combined left ventricular assist device and clenbuterol therapy. Circulation 2005, 112: 146–50.CrossRefGoogle Scholar
- 7.Saccà L, Napoli R, Cittadini A. Growth hormone, acro-megaly, and heart failure: an intricate triangulation. Clin Endocrinol (Oxf) 2003, 59: 660–71.CrossRefGoogle Scholar
- 8.Yang R, Bunting S, Gillett N, Clark R, Jin H. Growth hormone improves cardiac performance in experimental heart failure. Circulation 1995, 92: 262–7.PubMedCrossRefGoogle Scholar
- 9.Isgaard J, Kujacic V, Jennische E, et al. Growth hormone improves cardiac function in rats with experimental myocardial infarction. Eur J Clin Invest 1997, 27: 517–25.PubMedCrossRefGoogle Scholar
- 10.Jin H, Yang R, Gillett N, Clark RG, Ko A, Paoni NF. Beneficial effects of growth hormone and insulin-like growth factor-1 in experimental heart failure in rats treated with chronic ACE inhibition. J Cardiovasc Pharmacol 1995, 26: 420–5.PubMedCrossRefGoogle Scholar
- 11.Omerovic E, Bollano E, Mobini R, et al. Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts. Endocrinology 2000, 141: 4592–9.PubMedGoogle Scholar
- 12.Cittadini A, Isgaard J, Monti MG, et al. Growth hormone prolongs survival in experimental postinfarction heart failure. J Am Coll Cardiol 2003, 41: 2154–63.PubMedCrossRefGoogle Scholar
- 13.Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996, 334: 809–14.PubMedCrossRefGoogle Scholar
- 14.Genth-Zotz S, Zotz R, Geil S, Voigtländer T, Meyer J, Darius H. Recombinant growth hormone therapy in patients with ischemic cardiomyopathy: effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity. Circulation 1999, 99: 18–21.PubMedCrossRefGoogle Scholar
- 15.Isgaard J, Bergh CH, Caidahl K, Lomsky M, Hjalmarson A, Bengtsson BA. A placebo-controlled study of growth hormone in patients with congestive heart failure. Eur Heart J 1998, 19: 1704–11.PubMedCrossRefGoogle Scholar
- 16.Osterziel KJ, Strohm O, Schuler J, et al. Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet 1998, 351: 1233–7.PubMedCrossRefGoogle Scholar
- 17.Isgaard J, Bergh CH. Clinical potential of growth hormone in the treatment of congestive heart failure. BioDrugs 1999, 12: 245–50.PubMedCrossRefGoogle Scholar
- 18.Borthne K, Langslet A, Lindberg H, Skomedal T, Osnes JB. Differential recruitment of alpha 1- and beta-adrenoceptors in inotropic control of atrial child myocardium by endogenous noradrenaline. Acta Physiol Scand 2000, 170: 21–31.PubMedCrossRefGoogle Scholar
- 19.Hoffman JI, Kaplan S, Liberthson RR. Prevalence of congenital heart disease. Am Heart J 2004, 147: 425–39.PubMedCrossRefGoogle Scholar
- 20.Kaulitz R, Hofbeck M. Current treatment and prognosis in children with functionally univentricular hearts. Arch Dis Child 2005, 90: 757–62.PubMedCentralPubMedCrossRefGoogle Scholar
- 21.Report of the British Cardiac Society Working Party. Grown-up congenital heart (GUCH) disease: current needs and provision of service for adolescents and adults with congenital heart disease in the UK. Heart 2002, 88(Suppl 1): 11–14.Google Scholar
- 22.McElhinney DB, Colan SD, Moran AM, et al. Recombinant human growth hormone treatment for dilated cardiomyopathy in children. Pediatrics 2004, 114: e452–8.PubMedCrossRefGoogle Scholar
- 23.Cittadini A, Ines Comi L, Longobardi S, et al. A preliminary randomized study of growth hormone administration in Becker and Duchenne muscular dystrophies. Eur Heart J 2003, 24: 664–72.PubMedCrossRefGoogle Scholar
- 24.Rosti L, Cerini E, Festa P, Miola A, Brunelli V, Frigiola A. Lack of effects of recombinant human growth hormone in a child with a complex cardiovascular malformation and dilated cardiomyopathy. J Endocrinol Invest 2000, 23: 28–30.PubMedCrossRefGoogle Scholar