抵抗素促进内皮细胞激活:进一步证实了阿迪波金-内皮细胞相互作用的证据
Subodh Verma1, Shu-Hong Li, Chao-Hung Wang
1Division of Cardiac Surgery, Toronto General Hospital, 14EN-215, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4. subodh.verma@sympatico.ca
Circulation
|July 23, 2003
概括
脂肪细胞中的激素抵抗素直接激活内皮细胞 (ECs),通过增加内皮蛋白-1 (ET-1) 释放和促进ECs来激活内皮细胞.
科学领域:
- 内分泌学和新陈代谢学
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
背景情况:
- 脂肪细胞衍生的激素,如抵抗素,与胰岛素抵抗与心血管疾病的联系有关.
- 耐斯是一种新型阿迪波金,在代谢和心血管病理中具有潜在的作用.
研究的目的:
- 调查抵抗素对内皮细胞激活的直接影响.
- 阐明抵抗素影响内皮细胞功能的分子机制.
主要方法:
- 人类复合抵抗素被用于治疗内皮细胞 (ECs).
- 测试测量了内甲素-1 (ET-1) 释放,ET-1 mRNA表达和氧化 (NO) 生产.
- 基因记者测定了对ET-1促进体活性,包括AP-1位点功能,评估了抵抗素的作用.
- 评估了血管细胞粘附分子 (VCAM-1),单细胞化学吸引化学基因 (MCP-1) 和瘤亡因子受体相关因子-3 (TRAF3) 的表达水平.
主要成果:
- 耐斯在EC中显著增加ET-1释放和ET-1mRNA表达,而不会影响NO的产生.
- 抵抗剂增强了ET-1促进剂活性,依赖于AP-1转录因子结合部位.
- 抵抗上调的VCAM-1和MCP-1表达,同时降低TRAF3表达.
- 由CD40连接体诱导的抗药强化MCP-1生产.
结论:
- 抵抗素通过增加ET-1释放,部分通过AP-1位点激活,直接促进内皮细胞激活.
- 抵抗素对促炎粘附分子和化基因 (VCAM-1,MCP-1) 进行上调,对CD40信号传递的抑制剂TRAF3进行下调.
- 这些发现表明,抵抗素在机械上与代谢综合征中的心血管疾病发展有关.
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