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通过干扰CREB1-MDH1B-酸轴,OX-LDL会导致血管内皮损伤

Chen Pu¹, Hailang Yang², Guorong Wang¹

¹Department of Vascular Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.

Free radical biology & medicine

|January 10, 2026

概括

氧化LDL通过CREB1-MDH1B途径破坏马拉酸代谢,从而损害内皮功能,导致线粒体功能障碍. 针对这个轴可能为动脉样硬化提供治疗策略.

科学领域:

心血管生物学心血管生物学
分子代谢的分子代谢.
内皮细胞功能内皮细胞功能

背景情况:

动脉样硬化 (AS) 是一种普遍的心血管疾病,其中内皮功能障碍是关键的发起事件.
氧化低密度脂蛋白 (ox-LDL) 是血管损伤的主要致病因素,但其对细胞能量代谢的影响尚未完全理解.

研究的目的:

为了阐明ox-LDL如何通过抑制转录因子CREB1及其向基因MDH1B来损害内皮功能.
为了研究由此导致的酸盐代谢和线粒体功能障碍的破坏.
为了确定血管损伤的潜在治疗点.

主要方法:

对基因表达数据集 (GSE13139) 的分析和对人类大动脉内皮细胞 (HAEC) 的验证.
通过分子生物学技术 (RT-qPCR,西方抹黑,光酶试验,ChIP-qPCR) 调查CREB1-MDH1B的转录调节.
在小鼠模型中验证的代谢参数 (酸盐,ATP,ADP),线粒体功能 (膜潜力) 和超结构的测量.

主要成果:

氧-LDL抑制了CREB1的活性,导致MDH1B的表达减少,酸盐的产生受损,线粒体膜潜能降低,ATP水平降低.
过度表达MDH1B通过恢复酸盐水平和线粒体功能来改善ox-LDL诱导的内皮损伤.
外源性酸盐部分挽救了代谢缺陷,但没有恢复CREB1-MDH1B通路.

结论:

氧化LDL通过抑制CREB1,抑制MDH1B转录,破坏马拉酸代谢,并导致线粒体功能障碍,损害内皮细胞.
CREB1-MDH1B-酸盐轴将转录调节与内皮细胞中的代谢平衡联系起来.
这一途径代表了ox-LDL诱导的血管损伤的潜在治疗标.

关键词:

动脉样硬化是一种动脉样硬化.在CREB1中,CREB1是指CREB1,CREB1是指CREB1,CREB1是指CREB1.MDH1B MDH1B MDH1B MDH1B MDH1B MDH1B MDH1B MDH1B MDH1B MDH1B MDH1 马拉酸盐是什么意思马拉酸盐线粒体损伤是指线粒体损伤.ox-LDL 的使用情况.

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