Hostname: page-component-848d4c4894-wzw2p Total loading time: 0 Render date: 2024-06-09T16:01:02.764Z Has data issue: false hasContentIssue false

Molecular characterisation of neonatal cardiac hypertrophy and its regression

Published online by Cambridge University Press:  21 January 2005

Bamini Gopinath
Affiliation:
Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, and Central Clinical School, The University of Sydney, Australia
Ronald J. Trent
Affiliation:
Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, and Central Clinical School, The University of Sydney, Australia
Bing Yu
Affiliation:
Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, and Central Clinical School, The University of Sydney, Australia

Abstract

Neonatal cardiac hypertrophy associated with diabetic pregnancy is transient and regresses naturally, but is associated with increased morbidity and mortality.

This study was undertaken to analyse the changes in expression of 5 cardiac genes, including atrial natriuretic peptide, α- and β-myosin heavy chain, and cardiac and skeletal α-actin genes, using a rat neonatal model, in which cardiac hypertrophy was induced via maternal diabetes.

In the hypertrophied left ventricle of neonates from diabetic mothers, the levels of mRNA from all the above genes except skeletal α-actin were increased by between 1.8- and 12-fold compared with the controls at birth (p < 0.05). In the first 28 days, the level of mRNA for α-myosin heavy chain increased slightly, while that for atrial natriuretic peptide and β-myosin heavy chain decreased continuously similar to the controls, but at a significantly faster rate. No significant difference between the two groups of neonates was observed in all 5 genes after 1 month, indicating complete regression.

Expression of 5 cardiac genes in the neonatal cardiac hypertrophy was characterised in both hypertrophic and regressive phases. Hypertrophic regression provides a unique model for the testing of new drugs or genetic modifying factors in cardiac hypertrophy.

Type
Original Article
Copyright
© 2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Towbin JA, Lipshultz SE. Genetics of neonatal cardiomyopathy. Curr Opin Cardiol 1999; 14: 250262.Google Scholar
Lilien LD, Lilien RH, Setrakian S. Hemopericardium and cardiac tamponade as presenting findings of dexamethasone-induced hypertrophic cardiomyopathy complicated by transmural myocardial infarction. Pediatr Cardiol 2003; 24: 280283.Google Scholar
Bensky AS, Kothadia JM, Covitz W. Cardiac effects of dexamethasone in very low birth weight infants. Pediatrics 1996; 97: 818821.Google Scholar
Weintrob N, Karp M, Hod M. Short- and long-range complications in offspring of diabetic mothers. J Diabetes Complications 1996; 10: 294301.Google Scholar
Yunis KA, Bitar FF, Hayek P, Mroueh SM, Mikati M. Transient hypertrophic cardiomyopathy in the newborn following multiple doses of antenatal corticosteroids. Am J Perinatol 1999; 16: 1721.Google Scholar
Miller HC, Wilson HM. Macrosomia, cardiac hypertrophy, erythroblastosis and hyperplasia of the islets of Langerhans in infants born to diabetic mothers. J Pediatr 1943; 23: 251266.Google Scholar
Farquhar JW. The child of the diabetic woman. Arch Dis Child 1959; 34: 7696.Google Scholar
Garner P. Type I diabetes mellitus and pregnancy. Lancet 1995; 346: 157161.Google Scholar
Loffredo CA, Wilson PD, Ferencz C. Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology 2001; 64: 98106.Google Scholar
Zielinsky P, da Costa MH, Oliveira LT, Bonow FP, da Silva NI, Hagemann LL. Natural history of myocardial hypertrophy and its association with hyperinsulinism in infants of diabetic mothers. Arq Bras Cardiol 1997; 69: 389394.Google Scholar
Lesnik JJ, Singh GK, Balfour IC, Wall DA. Steroid-induced hypertrophic cardiomyopathy following stem cell transplantation in a neonate: a case report. Bone Marrow Transplant 2001; 27: 11051108.Google Scholar
Takino Y, Iwasaki T, Suzuki T. The cardiomyopathy in infants of streptozotocin-induced diabetic female rats. Jpn Circ J 1990; 54: 15541562.Google Scholar
Muangmingsuk S, Ingram P, Gupta MP, Arcilla RA, Gupta M. Dexamethasone induced cardiac hypertrophy in newborn rats is accompanied by changes in myosin heavy chain phenotype and gene transcription. Mol Cell Biochem 2000; 209: 165173.Google Scholar
Menezes HS, Barra M, Bello AR, Martins CB, Zielinsky P. Fetal myocardial hypertrophy in an experimental model of gestational diabetes. Cardiol Young 2001; 11: 609613.Google Scholar
Schwartz K, Carrier L, Chassagne C, Wisnewsky C, Boheler KR. Regulation of myosin heavy chain and actin isogenes during cardiac growth and hypertrophy. Symp Soc Exp Biol 1992; 46: 265272.Google Scholar
Vikstrom KL, Bohlmeyer T, Factor SM, Leinwand LA. Hypertrophy, pathology, and molecular markers of cardiac pathogenesis. Circ Res 1998; 82: 773778.Google Scholar
Lim HW, De Windt LJ, Mante J, et al. Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition. J Mol Cell Cardiol 2000; 32: 697709.Google Scholar
Sussman MA, Lim HW, Gude N, et al. Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science 1998; 281: 16901693.Google Scholar
Yu B, Pugazhenthi S, Khandelwal RL. Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes. Biochem Pharmacol 1994; 48: 949954.Google Scholar
Ramakers C, Ruijter JM, Deprez RH, Moorman AF. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 2003; 339: 6266.Google Scholar
Livak KJ. ABI Prism 7700 Sequence Detection System. User Bulletin 2: Applied Biosystem, 2001, pp 236.Google Scholar
Lisowski LA, Verheijen PM, De Smedt MM, Visser GH, Meijboom EJ. Altered fetal circulation in type-1 diabetic pregnancies. Ultrasound Obstet Gynecol 2003; 21: 365369.Google Scholar
Wentzel P, Ejdesjo A, Eriksson UJ. Maternal diabetes in vivo and high glucose in vitro diminish GAPDH activity in rat embryos. Diabetes 2003; 52: 12221228.Google Scholar
Patel P, Boyd CA, Johnston DG, Williamson C. Analysis of GAPDH as a standard for gene expression quantification in human placenta. Placenta 2002; 23: 697698.Google Scholar
Zhong H, Simons JW. Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem Biophys Res Commun 1999; 259: 523526.Google Scholar
Winer J, Jung CK, Shackel I, Williams PM. Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 1999; 270: 4149.Google Scholar
Boheler KR, Carrier L, Chassagne C, de la Bastie D, Mercadier JJ, Schwartz K. Regulation of myosin heavy chain and actin isogenes expression during cardiac growth. Mol Cell Biochem 1991; 104: 101107.Google Scholar
Day DA, Tuite MF. Post-transcriptional gene regulatory mechanisms in eukaryotes: an overview. J Endocrinol 1998; 157: 361371.Google Scholar