Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis

Nicolas Perrot, Vincenza Valerio, Donato Moschetta, S. Matthijs Boekholdt, Christian Dina, Hao Yu Chen, Erik Abner, Andreas Martinsson, Hasanga D. Manikpurage, Sidwell Rigade, Romain Capoulade, Elvira Mass, Marie Annick Clavel, Thierry Le Tourneau, David Messika-Zeitoun, Nicholas J. Wareham, James C. Engert, Gianluca Polvani, Philippe Pibarot, Tõnu EskoJ. Gustav Smith, Patrick Mathieu, George Thanassoulis, Jean Jacques Schott, Yohan Bossé, Marina Camera, Sébastien Thériault, Paolo Poggio, Benoit J. Arsenault

Research output: Contribution to journalArticlepeer-review

Abstract

The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with noncarriers. PCSK9 expression was higher in the aortic valves of patients CAVS compared with control patients. In human valve interstitials cells submitted to a pro-osteogenic medium, PCSK9 levels increased and a PCSK9 neutralizing antibody significantly reduced calcium accumulation.

Original languageEnglish
Pages (from-to)649-661
Number of pages13
JournalJACC: Basic to Translational Science
Volume5
Issue number7
DOIs
Publication statusPublished - Jul 2020

Keywords

  • aortic valve interstitial cell
  • apolipoprotein B
  • calcific aortic valve stenosis
  • LDL cholesterol
  • lipoprotein(a)
  • proprotein convertase subtilisin/kexin type 9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis'. Together they form a unique fingerprint.

Cite this