Overexpression of transforming growth factor-beta1 and insulin-like growth factor-I in patients with idiopathic hypertrophic cardiomyopathy.
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-beta1 (TGF-beta1), 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).


RESULTS
Levels of TGF-beta1, 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-beta and IGF-I were used to localize their peptides within the myocardium. Antisense and sense (control) cRNA probes of TGF-beta1 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-beta1 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-beta1 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-beta1 and IGF-I in the HCM cardiomyocytes.


CONCLUSIONS
Gene expression of TGF-beta1 and IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be associated with its development.
Li
R K
RK
Department of Clinical Biochemistry, and The Centre for Cardiovascular Research, The Toronto Hospital-General Division, University of Toronto, Ontario, Canada. rli@torhosp.toronto.on.ca
Li
G
G
Mickle
D A
DA
Weisel
R D
RD
Merante
F
F
Luss
H
H
Rao
V
V
Christakis
G T
GT
Williams
W G
WG
D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I