17 beta-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 17 beta -estradiol (E-2) 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 muM lysoPC increased the incorporation of [H-3]thymidine in VSMC obtained from female rats. 17 beta -E-2 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 17 alpha -E-2, 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 17 beta -E-2, ICI 182,780, or 17 alpha -E-2 as well as by N-acetyl-L-cysteine. Conclusion: 17 beta -E-2 inhibits in vitro VSMC proliferation induced by lysoPC via a nongenomic antioxidant mechanism.