转基因小鼠的阿尔多斯特诱导的冠状动脉功能障碍涉及血管光滑肌细胞的激活 (BKCa) 通道
Marie-Lory Ambroisine1, Julie Favre, Patricia Oliviero
1Inserm U689 and Paris Diderot University, Paris, France.
Circulation
|November 7, 2007
概括
在小鼠中,阿尔多的过度表达减少了血管中的激活 (BKCa) 通道,损害了冠状动脉放松. 这表明BKCa通道是心血管疾病的潜在治疗点.
科学领域:
- 心血管生理学心血管生理学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 心肌细胞中阿尔多胺合成酶过度表达会导致氧化独立的冠状动脉功能障碍.
- 激活 (BKCa) 通道对于血管光滑肌细胞 (VSMC) 放松至关重要.
研究的目的:
- 调查阿尔多素是否会改变VSMC中的BKCa通道表达或功能.
- 确定BKCa通道在阿尔多素诱导的冠状动脉功能障碍中的作用.
主要方法:
- 隔离的小鼠冠状动脉片段被用于线程肌图.
- 在使用和不使用各种抑制剂 (迪克洛菲纳克,卡里布托克辛,阿帕明,伊贝里托克辛) 评估了乙胆诱导的放松作用.
- 在心脏和冠状动脉中,BKCa通道表达量化通过qPCR和Western blot;在培养的老鼠大动脉VSMC中也研究了效应.
主要成果:
- 在MAS小鼠中,乙胆介导的冠状动脉放松显著减少,而螺旋拉克则阻止了.
- 在MAS小鼠心脏和冠状动脉中,BKCa通道子单位表达 (α和β1) 减少.
- 阿尔多斯特在培养的VSMC中降低了BKCa表达,这种效应被螺旋诺拉克阻止.
结论:
- 阿尔多的过度表达改变了VSMC的BKCa表达和BKCa依赖的冠状动脉放松.
- 这些变化可能会导致阿尔多斯在心血管疾病中的有害作用.
- BKCa通道代表了心血管疾病的潜在治疗点.
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