OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND INSULIN-LIKE GROWTH-FACTOR-I IN PATIENTS WITH IDIOPATHIC HYPERTROPHIC CARDIOMYOPATHY

Background Idiopathic hypertrophic cardiomyopathy (HCM) is characteriz ed by regional myocardial hypertrophy. To investigate involvement of g rowth factors on myocardial hypertrophy in HCM patients, we evaluated gene expression and cellular localization of transforming growth facto r-beta 1 (TGF-beta 1), 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 card iomyopathy (TM) (n=7). Methods and Results Levels of TGF-beta 1, IGF-I , IGF-II, and PDGF-B transcripts were quantified with the use of multi plex RT-PCR. Glyceraldehyde 3-phosphate dehydrogenase was used as an i nternal standard. Antibodies against TGF-beta and IGF-I were used to l ocalize their peptides within the myocardium. Antisense and sense (con trol) cRNA probes of TGF-beta 1 and IGF-I, labeled with digoxigenin, w ere used to localize the growth factor transcripts by in situ hybridiz ation. mRNA levels (densitometric ratio of growth factor/glyceraldehyd e-3-phosphate dehydrogenase) of TGF-beta 1 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-beta 1 and IGF-I in the hypertro phic AS myocardium were greater (P=.02, P=.05) than those in the expla nted myocardium (TM). Immunohistochemical and in situ hybridization st udies showed increased expression of TGF-beta 1 and IGF-I in the HCM c ardiomyocytes. Conclusions Gene expression of TGF-beta 1 and IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be associa ted with its development.