大麻素受体2-中心分子反循环驱动糖尿病心脏损伤的死亡
Pan Gao1, Mengying Cao1, Xueli Jiang1
1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, China (P.G., M.C., X.J., X.W., G.Z., C.Y., J.G., Y.Z.).
Circulation
|November 30, 2022
概括
一种被编程细胞死亡的形式, 驱动糖尿病心脏功能障碍. 向大麻素受体2 (CB2R) 为这种疾病提供了一个有前途的治疗策略.
科学领域:
- 心血管生物学
- 代谢疾病研究
- 细胞死亡机制
背景情况:
- 糖尿病性心脏功能障碍是糖尿病的重要并发症,主要是由细胞死亡驱动的.
- 糖尿病心脏细胞死亡的确切时间和序列尚不清楚.
- 确定特定的细胞死亡类型和治疗干预点对于治疗糖尿病心肌病至关重要.
研究的目的:
- 确定导致糖尿病心脏功能障碍的特定细胞死亡途径.
- 了解调节细胞死亡的分子机制.
- 提出一种针对糖尿病心脏病的新疗法.
主要方法:
- 使用1型和2型糖尿病小鼠模型 (db/db,HFD/STZ,STZ诱导).
- 在不同年龄的糖尿病小鼠心脏中评估了亡和亡.
- 使用G蛋白结合受体药物库,药理/基因调制,稳定细胞系和定制化抗体进行机理研究.
主要成果:
- 在糖尿病的晚期阶段,死细胞亡被激活,并直接导致心脏功能障碍.
- 大麻素受体2 (CB2R) 被确定为死亡的关键调节者.
- CB2R通常通过BACH2抑制亡;高葡萄糖通过促进CB2R内化和随后的MLKL介导酸化和CB2R降解来破坏这一过程,从而产生反循环.
结论:
- 一个涉及CB2R和BACH2的新型分子调节循环控制了糖尿病心脏中的亡.
- 而MLKL的激活则导致CB2R的酸化和降解,形成负反机制.
- 针对CB2R中心的亡途径为糖尿病心脏功能障碍提供了一个有前途的治疗策略.
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