Elevated insulin-like growth factor-I and transforming growth factor-beta 1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy. A …
G Li, RK Li, DA Mickle, RD Weisel, F Merante, WT Ball… - Circulation, 1998 - europepmc.org
G Li, RK Li, DA Mickle, RD Weisel, F Merante, WT Ball, GT Christakis, RJ Cusimano…
Circulation, 1998•europepmc.orgBackground Idiopathic hypertrophic obstructive cardiomyopathy (HOCM) is characterized by
regional myocardial hypertrophy. In our previous study, we demonstrated that mRNA levels
for insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta 1)
were elevated in HOCM tissue. In this study, we investigated IGF-I and TGF-beta 1 protein
levels and their respective receptor levels and localization. Methods and results Myocardial
growth factor protein levels were quantified with the use of chemiluminescent slot blot …
regional myocardial hypertrophy. In our previous study, we demonstrated that mRNA levels
for insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta 1)
were elevated in HOCM tissue. In this study, we investigated IGF-I and TGF-beta 1 protein
levels and their respective receptor levels and localization. Methods and results Myocardial
growth factor protein levels were quantified with the use of chemiluminescent slot blot …
Background
Idiopathic hypertrophic obstructive cardiomyopathy (HOCM) is characterized by regional myocardial hypertrophy. In our previous study, we demonstrated that mRNA levels for insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta 1) were elevated in HOCM tissue. In this study, we investigated IGF-I and TGF-beta 1 protein levels and their respective receptor levels and localization.
Methods and results
Myocardial growth factor protein levels were quantified with the use of chemiluminescent slot blot analysis with monoclonal antibodies against IGF-I and TGF-beta. The growth factor receptor binding sites were evaluated with 125I-labeled IGF-I and TGF-beta 1. The receptors were localized with immunohistochemistry. Data were expressed as mean+/-SEM. IGF-I and TGF-beta protein levels in HOCM myocardium (351.8+/-46.5 and 17.4+/-2.0 ng/g tissue, respectively; n= 6) were significantly higher (P< 0.01 for all groups) than in non-HOCM myocardium obtained from patients with aortic stenosis (AS, 182.1+/-22.7 and 8.0+/-1.2 ng/g tissue, respectively; n= 5), stable angina (SA, 117.4+/-20.9 and 7.5+/-2.7 ng/g tissue, respectively; n= 5), and transplanted hearts (TM, 166.3+/-30.1 and 6.4+/-1.2 ng/g tissue, respectively; n= 5). Maximal and high-affinity binding sites for IGF-I receptor in the HOCM were greater (P< 0.01 and P< 0.05) than the levels in AS, SA, and TM. The maximal receptor binding sites for TGF-beta 1 in HOCM were greater (P< 0.05) than those for SA and TM. Immunohistochemistry demonstrated that IGF-I and TGF-beta 1 receptors were located on the cardiomyocytes and TGF-beta 1 receptors were located on the fibroblasts.
Conclusions
Increased IGF-I and TGF-beta 1 gene expression previously observed in HOCM myocardium results in elevated protein levels. IGF-I and TGF-beta 1 signals may be further amplified by increased receptor numbers on cardiomyocytes and fibroblasts. The data suggest a possible autocrine mechanism of IGF-I-stimulated cardiomyocyte hypertrophy and a paracrine mechanism of TGF-beta 1-stimulated extracellular matrix overproduction in HOCM.
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