自毒素-lysophosphatidic 酸受体 5 轴通过反应性氧物种信号唤起内皮功能障碍
Anna Janovicz1,2, Aliz Majer1, Mónika Kosztelnik1,2
1Institute of Translational Medicine, Semmelweis University, H-1094 Budapest, Hungary.
Experimental biology and medicine (Maywood, N.J.)
|October 14, 2023
概括
Lysophosphatidylcholine (LPC) 通过激活自毒素-lysophosphatidic 酸 (LPA) -LPA5受体通路来破坏血管放松. 这一途径增加了活性氧物种,导致内皮功能障碍.
科学领域:
- 心血管生物学 心血管生物学
- 脂质代谢 脂质代谢是什么
- 内皮细胞功能 内皮细胞功能
背景情况:
- Lysophosphatidylcholine (LPC) 是一种涉及内皮功能障碍的生物活性脂质.
- 目前尚不清楚LPC诱导的内皮依赖性血管松的确切分子机制.
研究的目的:
- 研究LPC损害内皮依赖血管松的分子机制.
- 为了确定自毒素 (ATX) 和 lysophosphatidic acid (LPA) 受体在LPC引起的内皮功能障碍中的作用.
主要方法:
- 实验使用野生型 (WT) 鼠和各种 lysophosphatidic 酸受体淘汰 (KO) 鼠的大动脉环进行.
- 使用了ATX的药理抑制.
- 测量了乙胆 (ACh) 诱导的血管松.
- 评估了超氧化物脱酶的添加和过氧化 (H2O2) 的释放.
主要成果:
- 在WT小鼠中,LPC暴露显著降低了ACH诱导的血管松.
- 抑制ATX部分逆转了LPC诱导的内皮功能障碍.
- 在Lpar1,Lpar2和Lpar4KO小鼠中,LPC影响了血管松,但在Lpar5KO小鼠中,这种影响减弱了.
- 在WT容器中,LPC增加了H2O2的释放,在Lpar5KO小鼠中,这种效应减少了.
- 超氧化物失调酶在WT中减轻了LPC诱导的功能障碍,但在Lpar5KO小鼠中没有.
结论:
- 自毒素-溶酸-LPA5受体轴在LPC诱导的内皮功能障碍中起着至关重要的作用.
- 激活LPA5受体会调节活性氧物种的产生,导致血管松功能受损.
- 这项研究确定了一种新的途径,有助于LPC诱导的内皮功能障碍.
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