Pleiotropic Anti-atherosclerotic Effects of PCSK9 InhibitorsFrom Molecular Biology to Clinical Translation

Angelos D. Karagiannis, Martin Liu, Peter P. Toth, Shijia Zhao, Devendra K. Agrawal, Peter Libby, Yiannis S. Chatzizisis

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


Purpose of Review: Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors. Recent Findings: PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Summary: Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.

Original languageEnglish (US)
Article number20
JournalCurrent atherosclerosis reports
Issue number4
StatePublished - Apr 1 2018


  • Alirocumab
  • Anti-atherosclerotic effects
  • Atherosclerosis
  • Evolocumab
  • Inclisiran
  • PCSK9 inhibitors
  • Pleiotropic effects
  • Proprotein convertase subtilisin/kexin 9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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