依赖AMPK的YAP抑制调解了甲胺对肥胖相关的内皮功能障碍和炎症的保护作用
Lijing Kang1,2,3, Juanjuan Yi4, Chi-Wai Lau2
1Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China.
Antioxidants (Basel, Switzerland)
|September 28, 2023
概括
甲胺通过抑制YES相关蛋白1 (YAP) 激活来保护高葡萄糖诱导的血管功能障碍. 这项研究揭示了一个新的治疗点,AMPK-YAP-JNK轴,用于糖尿病心血管并发症.
科学领域:
- 心血管生物学 心血管生物学
- 代谢疾病 代谢疾病
- 分子细胞生物学 分子细胞生物学
背景情况:
- 高血糖和慢性炎症是心血管疾病的关键危险因素,特别是肥胖.
- 是的相关蛋白1 (YAP) 信号与高葡萄糖条件下的细胞功能障碍有关.
- 在糖尿病内皮功能障碍中metformin的血管保护作用中YAP的作用仍然不清楚.
研究的目的:
- 调查YAP激活在与肥胖相关的内皮功能障碍和炎症中的情况.
- 为了确定甲福明的血管保护作用是否通过YAP抑制进行介导.
- 在糖尿病血管并发症中探索AMPK-YAP-JNK信号轴.
主要方法:
- 重新分析了糖尿病患者临床测序数据.
- 在小鼠大动脉中对内皮依赖放松 (EDR) 的评估.
- 在高葡萄糖条件下使用人类静脉内皮细胞 (HUVEC) 的体外研究.
- 研究包括AMPK,YAP和JNK在内的信号通路.
主要成果:
- 在糖尿病血管组织中,YAP信号及其向基因 (CTGF,CYR61) 被上调.
- YAP过度表达会损害EDRs,并增加内皮细胞中的炎症和反应性氧物种.
- 高葡萄糖通过AMPK抑制激活YAP,导致JNK活性增加.
- 甲胺激活AMPK,促进YAP酸化,改善EDRs,并抑制JNK活动.
结论:
- YAP激活有助于高葡萄糖诱导的内皮功能障碍和炎症.
- 甲胺通过抑制AMPK-YAP-JNK轴而产生血管保护作用.
- 准AMPK-YAP-JNK通路为糖尿病血管并发症提供了潜在的治疗策略.
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