ENHANCED EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR-BETA RECEPTOR BY HIGH GLUCOSE - INVOLVEMENT OF PLATELET-DERIVED GROWTH-FACTOR IN DIABETIC ANGIOPATHY

Coronary heart disease is a major complication of diabetic subjects, a nd platelet-derived growth factor (PDGF) has been implicated in the de velopment of atherosclerosis. We investigated the effects of high gluc ose on expression of PDGF-beta receptor. In a binding assay with I-125 -labeled PDGF-BB homodimer, high concentrations of glucose increased h igh-affinity binding of PDGF-BB on human monocyte-derived macrophages and rabbit aortic medial smooth muscle cells. Northern blot analysis c onfirmed the enhanced effect of glucose on expression of PDGF-beta rec eptor mRNA in human monocyte-derived macrophages. The protein kinase C inhibitor, staurosporin, completely suppressed an increase in PDGF-BB binding by high glucose, and high glucose significantly activated pro tein kinase C. These results indicated that PDGF-beta receptor express ion was enhanced by high glucose through the activation of protein kin ase C. Furthermore, we observed similar effects of high glucose on bot h PDGF-beta receptor expression and protein kinase C activation in rat mesangial cells and human capillary endothelial cells. Our results su ggest that stimulation of the PDGF system is significantly involved in the development not only of diabetic atherosclerosis but also of micr oangiopathy.