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 smooth muscle cells (SMC) and is detected in SMC and macrophages in atherosclerotic plaques, suggesting that HB-EGF may be associated with the pathogenesis of atherosclerosis. The present study indicates that cilostazol, a phosphodiesterase III inhibitor, suppresses the expression of HB-EGF in rat aortic SMC and in U-937 cells, a macrophage-like cell line, stimulated by lipopolysaccharide. Further, cilostazol diminished the induction of HB-EGF mRNA by methylglyoxsal, which is a reactive dicarbonyl 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 conditioned medium of SMC. These data suggest that cilostazol might act by suppressing the progression of atherogenesis by means of suppressing the expression of HB-EGF in SMC and macrophages.
Kayanoki
Y
Y
Department of Biochemistry, Osaka University Medical School, Osaka, Suita, 565, Japan.
Che
W
W
Kawata
S
S
Matsuzawa
Y
Y
Higashiyama
S
S
Taniguchi
N
N
D000818:Animals; D002478:Cells, Cultured; D000077407:Cilostazol; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*
C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D004815:Epidermal Growth Factor; D000077407:Cilostazol