AKT 介质 适氨酸依赖于VSMC表型的调节
Abigail E Cullen1,2, Ann M Centner1, Riley Deitado1
1Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL 32306, USA.
阿迪波涅丁 (adipoq) 在血管光滑肌细胞 (VSMC) 功能和心血管健康中起着关键作用. 这项研究揭示了皮菌素如何通过AKT信号传递和细胞外矩阵调节来影响VSMC表型.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 亚迪波涅丁 (adipoq) 是心血管健康的关键激素,维护血管光滑肌细胞 (VSMC) 收缩功能.
- 之前的研究表明,关于阿迪波涅克丁在动脉样硬化中的作用的结果是相互矛盾的,这凸显了对更深入的机制理解的需要.
研究的目的:
- 阐明阿迪波涅丁调节VSMC表型和功能的分子机制.
- 研究阿迪波涅丁在AKT信号传递,细胞外基质 (ECM) 重塑和VSMCs内的代谢途径中的作用.
主要方法:
- 来自雄性大动脉的阿迪波内克丁缺乏 (adipoq) 和野生型VSMCs的RNA测序.
- 对包括AKT,AMPK和TGF-β在内的信号通路的分析.
- 评估线粒体功能,反应性氧物种 (ROS) 生产和ECM基因表达.
- 在体内分析大动脉蛋白表达,包括基于性别的差异.
主要成果:
- 皮菌素缺乏会提高AKT活动的调节,促进VSMC的增殖和迁移.
- AMPK激活部分缓解了增殖和迁移,但没有恢复收缩基因表达.
- 皮菌素缺乏会损害氧化酸化,增加糖解,并提高线粒体ROS.
- 亚迪波内丁通过对MMP2/9进行下调和对DCN/ELN进行上调来影响ECM重塑.
- 在体内观察到大动脉MMP3和DCN表达的显著性别差异.
结论:
- AKT/MAPK/TGF-β网络是VSMC表型的中央调节器,由皮菌素调节.
- 皮菌素缺乏导致VSMC功能和新陈代谢的有害变化,导致心血管病理.
- 了解这些途径为心血管疾病提供了潜在的治疗点.
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