Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis.

IF 1.5 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Clinical and Experimental Hypertension Pub Date : 2025-12-01 Epub Date: 2025-05-15 DOI:10.1080/10641963.2025.2506619

ChenKai Hu, FengXia Yuan, YingXing Wu, Shan Xiao, Yuan Xu, Xiang Peng, Lei He

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引用次数: 0

Abstract

Background: Pyroptosis is a novel kind of programmed cell death and Caspase-1 plays key roles in driving pyroptosis. The current study aims to elucidate the molecular mechanism affecting cardiomyocyte pyroptosis in myocardial ischemia/reperfusion (I/R) injury, both in vivo and in vitro.

Methods: A murine model of myocardial I/R injury was established and then treated with lentivirus-mediated shRNA targeting Caspase-1 to evaluate the effect of Caspase-1 on myocardial I/R injury. Further, Caspase-1 was silenced in the cardiomyocytes following hypoxia-reoxygenation (H/R) to detect the function of Caspase-1 in mitochondrial homeostasis and cardiomyocyte pyroptosis.

Results: Knockdown of Caspase-1 inhibited the secretion of interleukin-1 beta (IL-1β), improved cardiac dysfunction and decreased pyroptosis in vivo. The cardio-protective effect was verified in the H/R-induced cardiomyocyte model. Recombinant IL-1β protein reversed the inhibitory effect of Caspase-1 knockdown on pyroptosis.

Conclusion: Overall, activating the Caspase-1/IL-1β axis by myocardial I/R injury causes mitochondrial homeostasis imbalance, pyroptosis, and the consequent cardiomyocyte injury.

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caspase-1/IL-1β轴的破坏通过改善线粒体稳态和减少焦亡来减轻心肌缺血/再灌注损伤。

背景：焦亡是一种新型的程序性细胞死亡，Caspase-1在焦亡过程中起关键作用。本研究旨在从体内和体外两方面阐明心肌缺血再灌注（I/R）损伤中影响心肌细胞焦亡的分子机制。方法：建立小鼠心肌I/R损伤模型，用慢病毒介导靶向Caspase-1的shRNA处理，观察Caspase-1对心肌I/R损伤的影响。此外，在缺氧再氧化（H/R）后，在心肌细胞中沉默Caspase-1，以检测Caspase-1在线粒体稳态和心肌细胞焦亡中的功能。结果：敲低Caspase-1可抑制体内白细胞介素-1β (IL-1β)分泌，改善心功能障碍，减少焦亡。在H/ r诱导的心肌细胞模型中证实了其心脏保护作用。重组IL-1β蛋白逆转了Caspase-1敲低对焦亡的抑制作用。结论：总的来说，心肌I/R损伤激活Caspase-1/IL-1β轴可导致线粒体稳态失衡、焦亡和由此引起的心肌细胞损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Experimental Hypertension 医学-外周血管病

CiteScore

3.90

自引率

0.80%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.