PCSK9减弱了内皮细胞中的细胞分裂,并促进了血管衰老
Shijie Liu1,2, Jinzi Wu1, Amanda Stolarz3
1Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Theranostics
|June 7, 2023
概括
蛋白转化酶亚提利辛/素9型 (PCSK9) 损害了内皮细胞中的血细胞分裂,加速了血管衰老. 抑制PCSK9可恢复细胞增生并减轻衰老标志物,这表明它是血管健康的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 分子医学是分子医学.
背景情况:
- 蛋白转化酶亚素/素9型 (PCSK9) 和细胞分裂是血管衰老的关键调节者.
- PCSK9影响低密度脂蛋白受体水平,而细胞分裂会清除亡细胞.
- 这两种过程都与氧化还原生物学和炎症有关,这是血管衰老的关键因素.
研究的目的:
- 调查PCSK9对内皮细胞 (ECs) 中的细胞的影响.
- 探索PCSK9介导的血细胞衰老在血管衰老中的作用.
- 评估PCSK9抑制在老年血管系统中的治疗潜力.
主要方法:
- 研究使用了来自野生类型和PCSK9淘汰赛小鼠的初级人类和小鼠大动脉EC.
- 实验涉及复合PCSK9蛋白,PCSK9抑制 (Pep2-8),以及年轻和老年小鼠的分析.
- 关键的评估包括细胞测试,衰老标志物 (SA-β-gal),MerTK表达,蛋白质组学和免疫光.
主要成果:
- 重组PCSK9损害了EC细胞效应,并增加了SA-β-gal表达.
- 由于PCSK9的缺陷,恢复了乙细胞形成,并降低了SA-β-gal的活性.
- 在老年小鼠中,Pep2-8治疗改善了血细胞分裂,降低了NOX4,MAPK,NF-κB和促炎细胞因子的调节,同时提高了ENOS.
结论:
- 大动脉ECs进行了细胞分裂,这个过程被PCSK9.9减弱.
- PCSK9通过损害EC细胞增生而导致血管功能障碍和加快衰老.
- 抑制PCSK9代表了对抗血管衰老的有希望的策略.
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