title: 17Beta-estradiol inhibits proliferation of cultured vascular smooth muscle cells induced by lysophosphatidylcholine via a nongenomic antioxidant mechanism.
abstract: OBJECTIVE
  Lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, stimulates proliferation of vascular smooth muscle cells (VSMC). We investigated the direct impact of 17beta-estradiol (E2) on the proliferation of VSMC from rat aorta.
  
  
  RESULTS
  VSMC derived from both female and male rats expressed estrogen receptors alpha and beta. Treatments with 1% fetal bovine serum or 5 microM lysoPC increased the incorporation of [3H]-thymidine in VSMC obtained from female rats. 17Beta-E2 did not alter the response to fetal bovine serum, but significantly suppressed the enhanced deoxyribonucleic acid synthesis which had been induced by lysoPC in a dose-dependent manner (10(-4)-10(-6) M). Estrogen also inhibited the proliferation of VSMC from male animals. ICI 182,780, a specific estrogen receptor antagonist, and 17alpha-E2, an inactive form of estradiol, also decreased the mitogenic response to lysoPC in VSMC. In addition, N-acetyl-L-cysteine, a potent antioxidant, inhibited the lysoPC effect. Flow cytometric analysis using the oxidation-sensitive probe 2',7'-dichlorofluorescin diacetate revealed that elevated intracellular formation of reactive oxygen species elicited with lysoPC was depressed significantly by 17beta-E2, ICI 182,780, or 17alpha-E2 as well as by N-acetyl-L-cysteine.
  
  
  CONCLUSIONS
  17Beta-E2 inhibits in vitro VSMC proliferation induced by lysoPC via a nongenomic antioxidant mechanism.
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: B K
authors.initials: BK
authors.lastname: Yoon
authors.forename: W J
authors.initials: WJ
authors.lastname: Oh
authors.forename: B
authors.initials: B
authors.lastname: Kessel
authors.forename: C R
authors.initials: CR
authors.lastname: Roh
authors.forename: D
authors.initials: D
authors.lastname: Choi
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005312:Fetal Blood; D005434:Flow Cytometry; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D004958:Estradiol