THE EFFECT OF CILOSTAZOL, A CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE-III INHIBITOR, ON HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR EXPRESSION IN MACROPHAGES AND VASCULAR SMOOTH-MUSCLE CELLS

Heparin-binding EGF-like growth factor (HB-EGF) is a mitogen for smoot h muscle cells (SMC) and is detected in SMC and macrophages in atheros clerotic plaques, suggesting that HB-EGF may be associated with the pa thogenesis of atherosclerosis. The present study indicates that cilost azol, a phosphodiesterase III inhibitor, suppresses the expression of HB-EGF in rat aortic SMC and in U-937 cells, a macrophage-like cell li ne, stimulated by lipopolysaccharide. Further, cilostazol diminished t he induction of HB-EGF mRNA by methylglyoxsal, which is a reactive dic arbonyl metabolite produced as the result of a glycation reaction and which might be associated with macroangiopathy caused by hyperglycemia . Cilostazol suppressed the production of HB-EGF protein in the condit ioned medium of SMC. These data suggest that cilostazol might act by s uppressing the progression of atherogenesis by means of suppressing th e expression of HB-EGF in SMC and macrophages. (C) 1997 Academic Press .