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皮姆1诱发了内皮细胞到介质细胞的过渡,从而加剧了动脉样硬化

Zhiwei Xue^1,2, Mengtao Han^1,2, Tao Sun^1,2

¹Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Shandong, China.

|January 2, 2025

概括

这项研究确定了PIM1/P-NDRG1 ((S330) / PTBP1/EndMT通路作为动脉样硬化进展的关键驱动因素. 抑制这一轴为预防动脉样硬化的疾病提供了潜在的新策略.

科学领域:

分子生物学分子生物学
心血管研究研究心血管研究
细胞重编程细胞重编程

背景情况:

内皮细胞转换到介质细胞转换 (EndMT) 是一种细胞过程,与内皮细胞功能障碍有关,是动脉样硬化 (AS) 的关键因素.
EndMT有助于动脉样硬化病变的发展和斑块的不稳定性,但斑块微环境中的潜在机制尚未完全理解.

研究的目的:

在动脉样硬化背景下调查PIM1在EndMT机制中的作用.
阐明涉及PIM1促进AS进展的分子途径.

主要方法:

从饮食诱导的动脉样硬化小鼠模型中分析单细胞测序数据.
定量PCR,西部涂抹和免疫组织化学来评估PIM1表达.
使用通过腺相关病毒调节PIM1的ApoE-/-小鼠进行体内研究,以及对ox-LDL刺激的内皮细胞进行体内研究.
共同免疫沉以确定PIM1基质和组织学分析 (H&E,油红O,马森三色) 用于斑块特征.

主要成果:

随着AS的进展,内皮细胞中的PIM1表达增加.
内皮细胞特异性PIM1倒置减少了AS进展和EndMT,在体外减弱了ox-LDL诱导的EndMT.
在Ser330中,PIM1 knockdown降低了NDRG1的酸化,减少了NDRG1的核转位,并影响了NDRG1/PTBP1的相互作用,该相互作用调节了关键的EndMT标记物.
小分子Max-40279抑制了NDRG1酸化并抑制了EndMT.

结论:

PIM1/P-NDRG1 ((S330) / PTBP1/EndMT轴是促进动脉样硬化进展的关键途径.
针对这个轴,例如,用Max-40279,为预防AS提供了一个潜在的治疗策略.

关键词:

动脉样硬化是一种动脉样硬化.内皮细胞到介质细胞的过渡.马克斯-40279 的时间.核转位是指核转位.在PIM1中,PIM1是PIM1.

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