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Gustav Smith

Associate professor

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

Author

  • 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 Esko
  • J. Gustav Smith
  • Patrick Mathieu
  • George Thanassoulis
  • Jean Jacques Schott
  • Yohan Bossé
  • Marina Camera
  • Sébastien Thériault
  • Paolo Poggio
  • Benoit J. Arsenault

Summary, in English

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.

Department/s

  • Cardiology
  • Molecular Epidemiology and Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics
  • EpiHealth: Epidemiology for Health

Publishing year

2020

Language

English

Pages

649-661

Publication/Series

JACC: Basic to Translational Science

Volume

5

Issue

7

Document type

Journal article

Publisher

Elsevier

Topic

  • Cardiac and Cardiovascular Systems

Keywords

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

Status

Published

Research group

  • Molecular Epidemiology and Cardiology
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics

ISBN/ISSN/Other

  • ISSN: 2452-302X