Estradiol regulates monocyte chemotactic protein-1 in human coronary artery smooth muscle cells: a mechanism for its antiatherogenic effect
Estradiol regulates monocyte chemotactic protein-1 in human coronary artery smooth muscle cells: a mechanism for its antiatherogenic effect
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雌二醇调节人冠状动脉平滑肌细胞中的单核细胞趋化蛋白-1：其抗动脉粥样硬化作用的机制
作者：
E. Seli;B. Selam;G. Mor;U. Kayisli;T. Pehlivan;A. Arıcı
雌激素在动物模型中对早期动脉粥样硬化的保护作用已得到充分证实，但这种作用的机制尚不清楚。动脉粥样硬化发病机制中最早可识别的事件是动脉内皮下巨噬细胞的募集增加。巨噬细胞首先通过清除低密度脂蛋白发挥保护作用，但当胆固醇过量时，巨噬细胞转化为泡沫细胞并形成动脉粥样硬化。最近的人类和动物数据表明，巨噬细胞向动脉壁的募集是由单核细胞趋化蛋白-1（MCP-1）介导的。我们推测雌激素抗动脉粥样硬化的机制之一可能是下调动脉壁MCP-1的表达。设计人冠状动脉平滑肌细胞在添加生长因子和5%胎牛血清的平滑肌细胞基础培养基中增殖至汇合。在每个实验之前，将细胞与含有5%活性炭剥离的小牛血清的无酚红培养基孵育24小时，然后用不同浓度的17-雌二醇以及选择性雌激素受体（ER）调节剂雷洛昔芬和他莫昔芬处理。通过北方印迹定量MCP-1信使核糖核酸（mRNA）水平。使用酶联免疫吸附测定法定量MCP-1蛋白。逆转录-聚合酶链反应检测ER表达。结果人冠状动脉平滑肌细胞表达MCP-1 mRNA并产生MCP-1蛋白。在浓度为10−9 M或更高时，雌二醇对mRNA表达的抑制率高达40%。雷洛昔芬和他莫昔芬也导致抑制，但抑制作用小于雌二醇诱导时。依那普利还以浓度依赖性方式抑制MCP-1蛋白的产生（p < 0.05）。冠状动脉平滑肌细胞同时表达ER和ER。结论雌激素通过下调MCP-1的表达，减少巨噬细胞向动脉壁的聚集，从而预防动脉粥样硬化的发生。
ObjectiveThe protective effect of estrogen against early atherosclerosis in animal models is well documented, but the mechanisms responsible for this effect are not well understood. The earliest recognizable event in the pathogenesis of atherosclerosis is an increased recruitment of macrophages into the arterial subendothelium. Macrophages first play a protective role by removing low-density lipoproteins, but when the cholesterol is in excess, macrophages are converted into foam cells and form atheromas. Recent human and animal data indicate that the recruitment of macrophages to the arterial wall is mediated by monocyte chemotactic protein-1 (MCP-1). We hypothesized that one of the mechanisms of estrogen's protective effect against atherosclerosis may be the down-regulation of MCP-1 expression in the arterial wall. DesignHuman coronary artery smooth muscle cells were replicated to confluence in smooth muscle cell basal medium supplemented with growth factors and 5% fetal bovine serum. Before each experiment, cells were incubated for 24 h with phenol red-free medium containing 5% charcoal-stripped calf serum, and then they were treated with various concentrations of 17&bgr;-estradiol as well as selective estrogen receptor (ER) modulators, raloxifene and tamoxifen. MCP-1 messenger ribonucleic acid (mRNA) levels were quantified by Northern blots. MCP-1 protein was quantified using an enzyme-linked immunosorbent assay. ER expression was evaluated by reverse transcriptase-polymerase chain reaction. ResultsHuman coronary artery smooth muscle cells expressed MCP-1 mRNA and produced MCP-1 protein. Estradiol induced up to 40% inhibition in mRNA expression at concentrations 10−9 M and higher. Raloxifene and tamoxifen also resulted in an inhibition, but the inhibition was less than when induced by estradiol. Estradiol also inhibited the MCP-1 protein production in a concentration-dependent manner (p < 0.05). Coronary smooth muscle cells expressed both ER&agr; and ER&bgr;. ConclusionOur findings suggest that one of the mechanisms by which estrogen prevents atherosclerosis is by down-regulating MCP-1 expression, thus decreasing macrophage recruitment to the arterial wall.
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白卡诺鸽的早期动脉粥样硬化。
DOI：
--
发表时间：
1984
期刊：
The American journal of pathology
影响因子：
--
作者：
Jerome,WG;Lewis,JC
通讯作者：
Lewis,JC
影响因子：
158.5
作者：
COLDITZ, GA;WILLETT, WC;HENNEKENS, CH
通讯作者：
HENNEKENS, CH
影响因子：
15.9
作者：
SULLIVAN, TR;KARAS, RH;MENDELSOHN, ME
通讯作者：
MENDELSOHN, ME
影响因子：
20.1
作者：
T. Caulin–Glaser;G. Garcı́a-Cardeña;P. Sarrel;W. Sessa;J. Bender
通讯作者：
T. Caulin–Glaser;G. Garcı́a-Cardeña;P. Sarrel;W. Sessa;J. Bender
影响因子：
15.9
作者：
Gosling, J;Slaymaker, S;Charo, IF
通讯作者：
Charo, IF