17Beta-estradiol inhibits proliferation of cultured vascular smooth muscle cells induced by lysophosphatidylcholine via a nongenomic antioxidant mechanism.
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.
Yoon
B K
BK
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oh
W J
WJ
Kessel
B
B
Roh
C R
CR
Choi
D
D
Lee
J H
JH
Kim
D K
DK
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
D000975:Antioxidants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D004958:Estradiol