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REVIEW article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1413123
This article is part of the Research Topic Insights in Cardiovascular and Smooth Muscle Pharmacology: 2023 View all 9 articles

Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations

Provisionally accepted
Fengyuan Lu Fengyuan Lu En Li En Li Xiaoyu Yang Xiaoyu Yang *
  • Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China

The final, formatted version of the article will be published soon.

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily secreted by hepatocytes. PCSK9 is critical in liver low-density lipoprotein receptors (LDLRs) metabolism. In addition to its hepatocellular presence, PCSK9 has also been detected in cardiac, cerebral, islet, renal, adipose, and other tissues. Once perceived primarily as a "harmful factor," PCSK9 has been a focal point for the targeted inhibition of both systemic circulation and localized tissues to treat diseases. However, PCSK9 also contributes to the maintenance of normal physiological functions in numerous extrahepatic tissues, encompassing both LDLR-dependent and -independent pathways. Consequently, PCSK9 deficiency may harm extrahepatic tissues in close association with several pathophysiological processes, such as lipid accumulation, mitochondrial impairment, insulin resistance, and abnormal neural differentiation. This review encapsulates the beneficial effects of PCSK9 on the physiological processes and potential disorders arising from PCSK9 deficiency in extrahepatic tissues. This review also provides a comprehensive analysis of the disparities between experimental and clinical research findings regarding the potential harm associated with PCSK9 deficiency. The aim is to improve the current understanding of the diverse effects of PCSK9 inhibition.

    Keywords: pcsk9, PCSK9 deficiency, PCSK9 inhibition, PCSK9 monoclonal antibody, Low-density lipoprotein receptors

    Received: 06 Apr 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Lu, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiaoyu Yang, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China

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