KR 31372, a benzopyran derivative, inhibits oxidized LDL-stimulated proliferation and migration of vascular smooth muscle cells

KR 31372 is a benzopyran derivative. Both [H-3]thymidine incorporation and migrations (chemotactic and wound-edge) of cultured smooth muscle cells (SMCs) were greatly stimulated by oxidized low-density lipoprotein (LDL). These effects were significantly suppressed by KR 31372 (10(-7)-10(-6) M) and PDGF-BB antibody (10(-8)-10(-6) M). Preincubation with KR 31372 led to a decrease in the synthesis of PDGF-BB-like immunoreactivity (PDGF-BB-LI) that had been stimulated by oxidized LDL. Otherwise, KR 31372 and probucol strongly inhibited the production of thiobarbituric acid reactive substances (TBARS) caused by the incubation of LDL with Cu2+ ion, and significantly reduced the intracellular oxidative stress when stimulated with H2O2. Taken together, it is suggested that KR 31372 may inhibit the oxidized LDL-stimulated syntheses of DNA and PDGF-BB, and migration of the SMCs, in part, via the antioxidant activity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.