PCSK9 and infection: A potentially useful or dangerous association?

Farzad Khademi, Amir Abbas Momtazi-borojeni, Željko Reiner, Maciej Banach, Khalid Al Al-Rasadi, Amirhossein Sahebkar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Elevated plasma low-density lipoprotein-cholesterol (LDL-C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases (CVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid-independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis, and septic shock. Collected data from clinical trials revealed that treatment with PCSK9 inhibitors has beneficial effects in lowering LDL-C via inhibition of LDL-receptors (LDL-R), an antiviral effect on HCV infection via down-regulating the surface expression of LDL-R and CD81 on hepatic cells, and a positive association with increased inflammatory responses, as well as with septic shock by down-regulation of hepatocyte LDL-R. On the other hand, PCSK9 inhibition by therapeutic fully humanized antibodies has positive effects in reducing elevated LDL-C. However, their safety and tolerability is an important issue which has to be taken into consideration.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2017

Keywords

  • Cholesterol
  • Hepatitis C virus
  • Infection
  • LDL receptor
  • PCSK9

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Khademi, F., Momtazi-borojeni, A. A., Reiner, Ž., Banach, M., Al-Rasadi, K. A., & Sahebkar, A. (Accepted/In press). PCSK9 and infection: A potentially useful or dangerous association? Journal of Cellular Physiology. https://doi.org/10.1002/jcp.26040