Insulin-like growth factor I receptors in human cardiac myocytes and their relation to myocardial hypertrophy.

Specific binding sites for insulin-like growth factor I (IGF-I) and their expression during cardiac myocyte hypertrophy were studied by autoradiographic analysis of right ventricular biopsy specimens from patients with hypertrophic cardiomyopathy (9 cases), dilated cardiomyopathy (8 cases), and sick sinus syndrome (5 cases). Frozen specimens were cut into 5 microns-thick sections and thaw-mounted on albumin-coated slides. After incubation with [125I]IGF-I, with or without excess cold IGF-I, autoradiography was performed, and grains over myocytes were counted microscopically. Binding of [125I]IGF-I was inhibited in a dose-dependent manner by unlabeled IGF-I and competed for by IGF-I > IGF-II > insulin. The maximal grain density was higher in hypertrophic cardiomyopathy (186 +/- 47/1.8 x 10(-2) mm2) than in dilated cardiomyopathy (124 +/- 13/1.8 x 10(-2) mm2) or sick sinus syndrome (98 +/- 18/1.8 x 10(-2) mm2) (p < 0.01). There was a strong correlation between the maximal grain density and the diameter of right ventricular myocytes in hypertrophic cardiomyopathy (r = 0.83), but no similar correlation was observed in dilated cardiomyopathy or sick sinus syndrome. These data suggest that IGF-I receptors are present in adult human cardiac myocytes, and that IGF-I receptors are related to the development of myocyte hypertrophy in hypertrophic cardiomyopathy.