(Circulation. 1997;96:874-881.)
© 1997 American Heart Association, Inc.
Articles |
Overexpression of Transforming Growth Factor-ß1 and Insulin-Like Growth Factor-I in Patients With Idiopathic Hypertrophic Cardiomyopathy
From the Division of Cardiovascular Surgery, Department of Clinical Biochemistry, and The Centre for Cardiovascular Research, The Toronto Hospital–General Division, University of Toronto, Toronto, Ontario, Canada (R.-K.L., G.L., D.A.G.M., R.D.W., F.M., V.R., G.T.C., W.G.W.), and Institut für Pharmakologie und Toxikologie (H.L.), Westfälische Wilhelms–Universität Münster, Domagkstrasse 12, Münster, Germany.
Correspondence to Dr Ren-Ke Li, Toronto Hospital-General Division, CCRW 1-854, 200 Elizabeth St, Toronto, Ontario, Canada, M5G 2C4. E-mail rli{at}torhosp.toronto.on.ca
Background Idiopathic hypertrophic cardiomyopathy (HCM) is characterized by regional myocardial hypertrophy. To investigate involvement of growth factors on myocardial hypertrophy in HCM patients, we evaluated gene expression and cellular localization of transforming growth factor-ß1 (TGF-ß1), insulin-like growth factors (IGF-I and IGF-II), and platelet-derived growth factor-B (PDGF-B) in ventricular biopsies obtained from patients with HCM (n=8), aortic stenosis (AS) (n=8), or stable angina (SA) (n=8) and from explanted hearts with ischemic cardiomyopathy (TM) (n=7).
Methods and Results Levels of TGF-ß1, IGF-I, IGF-II, and PDGF-B transcripts were quantified with the use of multiplex RT-PCR. Glyceraldehyde 3-phosphate dehydrogenase was used as an internal standard. Antibodies against TGF-ß and IGF-I were used to localize their peptides within the myocardium. Antisense and sense (control) cRNA probes of TGF-ß1 and IGF-I, labeled with digoxigenin, were used to localize the growth factor transcripts by in situ hybridization. mRNA levels (densitometric ratio of growth factor/glyceraldehyde-3-phosphate dehydrogenase) of TGF-ß1 and IGF-I in HCM (0.75±0.05 and 0.85±0.15, respectively; mean±1 SEM) were significantly (P<.01 for all groups) elevated in comparison with non-HCM myocardium (AS: 0.38±0.07, 0.29±0.06; SA: 0.32±0.04, 0.18±0.05; TM: 0.25±0.03, 0.15±0.03). mRNA levels of TGF-ß1 and IGF-I in the hypertrophic AS myocardium were greater (P=.02, P=.05) than those in the explanted myocardium (TM). Immunohistochemical and in situ hybridization studies showed increased expression of TGF-ß1 and IGF-I in the HCM cardiomyocytes.
Conclusions Gene expression of TGF-ß1 and IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be associated with its development.
Key Words: cardiomyopathy • growth substances • hypertrophy • immunohistochemistry • molecular biology
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