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REVIEW article

Front. Cardiovasc. Med.
Sec. Atherosclerosis and Vascular Medicine
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1431398
This article is part of the Research Topic New Trends in Vascular Biology 2024 View all 8 articles

The role of proprotein convertase subtilisin/kexin 9 (PCSK9) in macrophage activation: a focus on its LDL receptor-independent mechanisms

Provisionally accepted
Shunsuke Katsuki Shunsuke Katsuki 1Prabhash K. Jha Prabhash K. Jha 2Elena Aikawa Elena Aikawa 2Masanori Aikawa Masanori Aikawa 3*
  • 1 Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Fukuoka, Japan
  • 2 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
  • 3 Cardiovascular Division and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

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

    Recent clinical trials demonstrated that proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors reduce cardiovascular events without affecting systemic inflammation in the patients with coronary artery disease, as determined by high sensitivity C-reactive protein (CRP) levels. However, its proinflammatory effects in cardiovascular disease in humans and experimental animals beyond the traditional cholesterol receptor-dependent lipid metabolism have also called attention of the scientific community. PCSK9 may target receptors associated with inflammation other than the low-density lipoprotein receptor (LDLR) and members of the LDLR family. Accumulating evidence suggests that PCSK9 promotes macrophage activation not only via lipid-dependent mechanisms, but also lipidindependent and LDLR-dependent or -independent mechanisms. In addition to dyslipidemia, PCSK9 may thus be a potential therapeutic target for various pro-inflammatory diseases. Deleted: P 29 Deleted: that regulates lipid metabolism by degradation of 30 the low-density lipoprotein receptors (LDLRs) in hepatocytes 31 has serves as a therapeutic target for hypercholesterolemia.

    Keywords: PCSK9 (proprotein convertase subtilisin/kexin type 9), Macrophages, Atherosclerosis, Inflammation, Vascular biology, Coronary artery diasease, LDL receptor (LDLR), Dyslipidemia

    Received: 11 May 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Katsuki, Jha, Aikawa and Aikawa. 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: Masanori Aikawa, Cardiovascular Division and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.