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阿司匹林通过调节LPCAT3来调节心血管疾病中促凝脂的产生
Majd B Protty1, Victoria J Tyrrell1, Ali A Hajeyah1
1Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
酶氧化脂 (eoxPL) 是原血栓的,并且在动脉样硬化心血管疾病 (ASCVD) 中发生变化. lysophosphatidylcholine酸转移酶3 (LPCAT3) 产生阿司匹林敏感的eoxPL,影响血栓形成的风险.
科学领域:
- 心血管研究研究心血管研究
- 脂质代谢 脂质代谢是什么
- 血栓形成生物学 血栓形成生物学
背景情况:
- 酶氧化脂 (eoxPL) 是前体质的,但它们在动脉疾病和治疗反应中的作用尚不清楚.
- 通过Lands循环形成eoxPL的特定乙转移酶仍然未被确定.
- 了解eoxPL生成对于管理心血管疾病 (CVD) 和血栓形成风险至关重要.
研究的目的:
- 在动脉样硬化心血管疾病 (ASCVD) 患者和人类动脉瘤中研究eoxPL生成.
- 确定包括阿司匹林在内的心血管治疗对eoxPL水平的影响.
- 为了确定负责特定eoxPL生物合成的乙转移酶.
主要方法:
- 从ASCVD患者和健康对照中的血小板和白细胞中量化eoxPL.
- 从不同解剖部位对人类动脉瘤中eoxPL的分析.
- 使用 lysophosphatidylcholine酸转移酶3 (LPCAT3) 抑制剂和无细胞试验的抑制研究.
- 在健康人群中评估阿司匹林对eoxPL的影响.
主要成果:
- 与对照组相比,ASCVD患者的血小板eoxPL概况发生了变化,COX衍生性较低,12-LOX-diacyleoxPL较高.
- 在健康受试者中服用阿司匹林补充剂重新总结了ASCVD患者观察到的改变的eoxPL特征.
- 抑制LPCAT3可以选择性地阻断12-LOX衍生的二甲基-eoxPL,将其确定为关键的乙基转移酶.
- 在四肢/冠状动脉血栓和动脉血栓之间,血小板eoxPL的特征有所不同.
结论:
- 在ASCVD中,EOXPL的含量和成分发生了显著的变化,并且受到阿司匹林治疗的影响.
- Lysophosphatidylcholine acyltransferase 3 (LPCAT3) 被确定为负责产生对阿司匹林敏感的12-LOX衍生的二甲基-eoxPL的乙烯转移酶.
- 这些发现突显了eoxPL在血细胞中发生的变化的临床意义,对于有血栓形成风险的人来说.
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