内皮细胞衍生的胆固醇结晶会促进动脉粥样硬化早期的内皮炎症。

IF 5.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Antioxidants & redox signaling Pub Date : 2024-08-01 Epub Date: 2024-04-10 DOI:10.1089/ars.2023.0498
Xia Wang, Wenxia Fu, Guo Zhou, Huanhuan Huo, Xin Shi, Hao Wang, Yinghua Wang, Xiying Huang, Linghong Shen, Long Li, Ben He
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引用次数: 0

摘要

目的:内皮炎症是动脉粥样硬化发生和发展的关键,而胆固醇结晶(CCs)在动脉粥样硬化发生中起着关键作用。然而,CCs 对内皮炎症的影响和起源还不十分清楚:结果:在本研究中,我们发现部分结扎的颈动脉内皮下间隙在西式饮食喂养一周后(免疫细胞浸润之前)才出现 CCs。在体外,人主动脉内皮细胞(HAECs)在LDL处理后产生了CCs。这些由 EC 衍生的 CC 增加了细胞间粘附分子-1(ICAM1)和血管细胞粘附分子-1(VCAM1)的表达。机理研究表明,CC 诱导的热蛋白沉积对内皮炎症至关重要。敲除 GSDMD 可抑制 CC 诱导的内皮炎症,减轻斑块进展并减少巨噬细胞含量。相应地,抑制 GSDMD 减少了 CC 诱导的 HAEC 中 VCAM1 和 ICAM1 的增加。此外,研究还发现 CC 介导的热凋亡依赖于 Caspase-1 (CASP1)。抑制 CASP1 还能减轻血管内皮炎症和斑块的进展。此外,GSDMD 在人类动脉粥样硬化斑块中的表达也有所增加。这些研究结果表明,EC源性CC可能是动脉粥样硬化发病机制的重要驱动力:创新:这项研究揭示了一种新的认识,即EC源性CC诱导的热蛋白沉积是早期动脉粥样硬化发生的一个关键初始因素:靶向内皮GSDMD或CASP1有助于抑制血管炎症和动脉粥样硬化的发生:靶向内皮 GSDMD 或 CASP1 有助于抑制血管炎症和动脉粥样硬化的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Endothelial Cell-Derived Cholesterol Crystals Promote Endothelial Inflammation in Early Atherogenesis.
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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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