KR 31372, a benzopyran derivative, inhibits oxidized LDL-stimulated proliferation and migration of vascular smooth muscle cells.
KR 31372 is a benzopyran derivative. Both [3H]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 H,O2. 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.
Kim
H H
HH
Department of Pharmacology, College of Medicine, Pusan National University, South Korea.
Ha
H J
HJ
Kim
S O
SO
Ki
S K
SK
Yoo
S E
SE
Hong
K W
KW
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D000077214:Becaplermin; D001578:Benzopyrans / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011341:Probucol / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011921:Rats, Inbred WKY
D000924:Anticholesteremic Agents; D000975:Antioxidants; D001578:Benzopyrans; C419651:KR 31372; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C099252:oxidized low density lipoprotein; D000077214:Becaplermin; D004247:DNA; D011341:Probucol