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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Objectives: Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17β-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. Methods: VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. Results: After pre-treatment for 24 hours, 17β-E2 suppressed lysoPC-induced (15 mM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17β-E2 (10−6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17β-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF- κB-mediated transcriptional activity were reduced with 17β-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. Conclusions: In cultured VSMCs treated with lysoPC, 17β-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.
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참고문헌 (25)
참고문헌 신청
Bennett MR / 2016 / Vascular smooth muscle cells in atherosclerosis / Circ Res 118:692~702
Kattoor AJ / 2017 / Oxidative stress in atherosclerosis / Curr Atheroscler Rep 19:42
Pant S / 2014 / Inflammation and atherosclerosis--revisited / J Cardiovasc Pharmacol Ther 19:170~178
Elmore S / 2007 / Apoptosis : a review of programmed cell death / Toxicol Pathol 35:495~516
McCarthy NJ / 2000 / The regulation of vascular smooth muscle cell apoptosis / Cardiovasc Res 45:747~755
Kattoor AJ / 2017 / Oxidative stress in atherosclerosis / Curr Atheroscler Rep 19:42
Pant S / 2014 / Inflammation and atherosclerosis--revisited / J Cardiovasc Pharmacol Ther 19:170~178
Elmore S / 2007 / Apoptosis : a review of programmed cell death / Toxicol Pathol 35:495~516
McCarthy NJ / 2000 / The regulation of vascular smooth muscle cell apoptosis / Cardiovasc Res 45:747~755
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