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PCSK9通过SIRT1通路影响血管衰老

Yuqin Wang¹, Shaoqing Cao¹, Zhangyu Wang¹

¹Department of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China.

Experimental gerontology

|February 8, 2025

概括

蛋白转化酶素9 (PCSK9) 抑制剂通过降低细胞sirtuin 1 (SIRT1) 水平来延缓血管衰老. 这种机制抑制了血管衰老,并减少了与衰老相关的蛋白质的表达.

科学领域:

心血管生物学心血管生物学
衰老研究研究衰老研究
分子医学是分子医学.

背景情况:

年龄是动脉样硬化心血管疾病的重要危险因素,增加了血管内脏厚度,内皮功能障碍和血栓形成.
驱动与年龄相关的血管损伤的精确机制仍然不完全理解.
细胞衰老在与年龄相关的血管病理中起着关键作用.

研究的目的:

调查蛋白转化酶素9 (PCSK9) 抑制剂对血管细胞和老年小鼠细胞衰老的影响.
阐明sirtuin 1 (SIRT1) 途径在PCSK9-介导的血管衰老中的作用.
为了确定PCSK9抑制是否可以减轻与年龄相关的血管功能障碍.

主要方法:

评估PCSK9抑制剂对人类静脉内皮细胞 (HUVEC) 和老年小鼠的影响.
利用脂聚糖 (LPS) 诱导PCSK9激活和细胞衰老.
测量了衰老标记物 (P16,P21,P53) 和SIRT1水平的表达.
研究了SIRT1通路调节 (抑制和激活) 对PCSK9诱导的衰老的影响.

主要成果:

抑制PCSK9在小鼠中延迟了衰老,并减少了血管衰老.
诱导LPS刺激了PCSK9的激活,增加了衰老标志物 (P16,P21,P53).
过度表达PCSK9加速衰老,促进氧化应激,并上调衰老相关基因.
抑制SIRT1减弱了PCSK9的衰老作用;SIRT1激活增强了衰老.

结论:

抑制PCSK9通过降低SIRT1表达的调节来缓解血管衰老.
PCSK9在血管系统中起着促进衰老的作用,部分通过SIRT1通路.
向PCSK9提供了一种潜在的治疗策略,以对抗与年龄相关的血管疾病.

关键词:

脂聚糖类糖化物脂聚糖类糖化物这是一种等离子体.蛋白转化酶亚素类型素9 小的干扰RNA可以干扰RNA.血管衰老是因为血管衰老.

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