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PANoptosis:心血管疾病的新靶点。

PANoptosis: a novel target for cardiovascular diseases.

机构信息

Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

出版信息

Trends Pharmacol Sci. 2024 Aug;45(8):739-756. doi: 10.1016/j.tips.2024.06.002. Epub 2024 Jul 12.

Abstract

PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death. Given the physiological relevance in several diseases, PANoptosis is a pivotal therapeutic target. Notably, previous research has primarily focused on the role of PANoptosis in cancer and infectious and inflammatory diseases. By contrast, its role in cardiovascular diseases has not been comprehensively discussed. Here, we review the available evidence on PANoptosis in cardiovascular diseases, including cardiomyopathy, atherosclerosis, myocardial infarction, myocarditis, and aortic aneurysm and dissection, and explore a variety of agents that target PANoptosis, with the overarching goal of providing a novel complementary approach to combatting cardiovascular diseases.

摘要

细胞焦亡是一种独特的先天免疫炎症性裂解细胞死亡途径,由先天免疫传感器启动,并由胱天蛋白酶和 RIPK 驱动。作为一种独特的途径,细胞焦亡的执行不能通过靶向其他细胞死亡途径(如细胞焦亡、细胞凋亡或坏死性凋亡)来阻止。相反,靶向关键的 PANoptosome 成分可以作为预防这种细胞死亡形式的策略。鉴于其在几种疾病中的生理相关性,细胞焦亡是一个关键的治疗靶点。值得注意的是,先前的研究主要集中在细胞焦亡在癌症和感染性及炎症性疾病中的作用。相比之下,其在心血管疾病中的作用尚未得到全面讨论。在这里,我们综述了细胞焦亡在心血管疾病中的现有证据,包括心肌病、动脉粥样硬化、心肌梗死、心肌炎和主动脉瘤和夹层,并探讨了多种靶向细胞焦亡的药物,以期为治疗心血管疾病提供一种新的补充方法。

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