Wang Huaru, Tang Guodong, Wu Jianqiang, Qin Xuzhen
Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
J Inflamm Res. 2025 Mar 30;18:4509-4532. doi: 10.2147/JIR.S509222. eCollection 2025.
In cardiovascular disease, the discovery of the proprotein convertase subtilisin/kexin type 9 (PCSK9) has undoubtedly opened a new chapter in regulating blood lipids. Since its first identification as a key regulator of low-density lipoprotein receptor (LDLR) degradation in 2003, the role of PCSK9 in cholesterol metabolism has been extensively studied. However, with further research, the pleiotropy of PCSK9 has gradually emerged, and its impact extends far beyond cholesterol metabolism in the liver. The purpose of this review is to systematically explore the pleiotropy of PCSK9, extending from its important role in lipid regulation to its extensive effects in extrahepatic tissues, and to reveal its potential role in cardiovascular health, nervous system function, and tumor biology. By integrating the latest research findings, this paper summarizes the complex mechanisms of action of PCSK9 in different biological processes and explores its potential and challenges as a therapeutic target.
在心血管疾病领域，前蛋白转化酶枯草溶菌素9型（PCSK9）的发现无疑为血脂调节开启了新篇章。自2003年首次被鉴定为低密度脂蛋白受体（LDLR）降解的关键调节因子以来，PCSK9在胆固醇代谢中的作用已得到广泛研究。然而，随着进一步研究，PCSK9的多效性逐渐显现，其影响远远超出了肝脏中的胆固醇代谢。本综述的目的是系统地探讨PCSK9的多效性，从其在脂质调节中的重要作用延伸到其在肝外组织中的广泛影响，并揭示其在心血管健康、神经系统功能和肿瘤生物学中的潜在作用。通过整合最新研究结果，本文总结了PCSK9在不同生物学过程中的复杂作用机制，并探讨了其作为治疗靶点的潜力和挑战。
