Estradiol suppresses MCP-1 expression in vivo - Implications for atherosclerosis
Estradiol suppresses MCP-1 expression in vivo - Implications for atherosclerosis
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DOI：
10.1161/01.atv.18.10.1575
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发表时间：
1998-10-01
影响因子：
8.7
通讯作者：
Nathan, L
中科院分区：
文献类型：
--
作者：
Pervin, S;Singh, R;Nathan, L
17 -雌二醇延缓动脉粥样硬化的机制尚不清楚。单核细胞与内皮细胞的粘附以及单核细胞向动脉壁的迁移是整个动脉粥样硬化过程中发生的关键细胞事件，可能对雌二醇有反应。单核细胞趋化蛋白-1 （MCP-1）是一种在动脉粥样硬化病变中表达的趋化因子，被认为在刺激血液单核细胞向动脉粥样硬化病变的迁移中起主要作用。因此，我们在体内评估了雌二醇对饲喂高胆固醇（0.5%）饲粮6周的家兔和饲喂正常饲料的家兔胸降主动脉MCP-1蛋白和mRNA表达的影响。Western blot法和单核细胞趋化性生物测定法定量MCP-1蛋白，逆转录-聚合酶链反应法测定MCP-1 mRNA表达水平。我们观察到，在卵巢完整和卵巢切除（OVX）动物中，高胆固醇饲料喂养6周后，MCP-1蛋白和mRNA的表达均显著增加。在补充雌二醇颗粒（1.5 mg和10.0 mg 60天释放颗粒）的OVX兔中，胆固醇诱导的MCP-1蛋白和mRNA表达的增加显著减弱，产生的雌二醇浓度范围接近生理水平。MCP-1蛋白和mRNA的表达在正常胆固醇水平的OVX家兔中与正常胆固醇水平的卵巢完整动物相比有所增加，而在补充雌二醇颗粒的OVX动物中，MCP-1蛋白和mRNA的表达没有增加。我们的观察表明，基础和高胆固醇血症引起的MCP-1蛋白的增加都受到雌二醇生理浓度的调节。
The mechanisms by which 17 beta-estradiol retards atherogenesis are not known. The adhesion of monocytes to endothelial cells followed by the migration of monocytes into the artery wall are key cellular events that occur throughout the entire atherogenic process and may be responsive to estradiol, Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is expressed in atherosclerotic lesions, is thought to play a major role in stimulating the migration of blood monocytes into developing atherosclerotic lesions. We therefore assessed the effects of estradiol in vivo on MCP-1 protein and mRNA expression in the descending thoracic aorta of rabbits fed a cholesterol-enriched (0.5%) diet for 6 weeks and in animals fed normal chow. MCP-1 protein was quantified by Western blot analysis and monocyte chemotaxis bioassay, and reverse transcription-polymerase chain reaction was used to ascertain the level of MCP-1 mRNA expression. We observed that in both ovary-intact and ovariectomized (OVX) animals, MCP-1 protein and mRNA expression were significantly increased by 6:weeks in animals fed a high-cholesterol diet. The cholesterol-induced increase in MCP-1 protein and mRNA expression was significantly attenuated in OVX rabbits supplemented with estradiol pellets (1.5- and 10.0-mg 60-day-release pellets), which yielded a range of estradiol concentrations encompassing the physiological levels. MCP-1 protein and mRNA expression were increased in normocholesterolemic OVX rabbits compared with normocholesterolemic ovary-intact animals, and this increase was prevented in OVX animals supplemented with estradiol pellets. Our observations indicate that both basal and hypercholesterolemia-induced increases in MCP-1 protein are modulated by physiological concentrations of estradiol.