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

Perrot, Nicolas ; Valerio, Vincenza ; Moschetta, Donato ; Boekholdt, S. Matthijs ; Dina, Christian ; Chen, Hao Yu ; Abner, Erik ; Martinsson, Andreas LU ; Manikpurage, Hasanga D. and Rigade, Sidwell , et al. (2020) In JACC: Basic to Translational Science 5(7). p.649-661
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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aortic valve interstitial cell, apolipoprotein B, calcific aortic valve stenosis, LDL cholesterol, lipoprotein(a), proprotein convertase subtilisin/kexin type 9
in
JACC: Basic to Translational Science
volume
5
issue
7
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:85087405073
  • pmid:32760854
ISSN
2452-302X
DOI
10.1016/j.jacbts.2020.05.004
language
English
LU publication?
yes
id
3c23e2f1-5101-4798-af05-5f7e4b4d1448
date added to LUP
2020-12-29 13:44:34
date last changed
2024-03-05 16:27:30
@article{3c23e2f1-5101-4798-af05-5f7e4b4d1448,
  abstract     = {{<p>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.</p>}},
  author       = {{Perrot, Nicolas and Valerio, Vincenza and Moschetta, Donato and Boekholdt, S. Matthijs and Dina, Christian and Chen, Hao Yu and Abner, Erik and Martinsson, Andreas and Manikpurage, Hasanga D. and Rigade, Sidwell and Capoulade, Romain and Mass, Elvira and Clavel, Marie Annick and Le Tourneau, Thierry and Messika-Zeitoun, David and Wareham, Nicholas J. and Engert, James C. and Polvani, Gianluca and Pibarot, Philippe and Esko, Tõnu and Smith, J. Gustav and Mathieu, Patrick and Thanassoulis, George and Schott, Jean Jacques and Bossé, Yohan and Camera, Marina and Thériault, Sébastien and Poggio, Paolo and Arsenault, Benoit J.}},
  issn         = {{2452-302X}},
  keywords     = {{aortic valve interstitial cell; apolipoprotein B; calcific aortic valve stenosis; LDL cholesterol; lipoprotein(a); proprotein convertase subtilisin/kexin type 9}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{649--661}},
  publisher    = {{Elsevier}},
  series       = {{JACC: Basic to Translational Science}},
  title        = {{Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis}},
  url          = {{http://dx.doi.org/10.1016/j.jacbts.2020.05.004}},
  doi          = {{10.1016/j.jacbts.2020.05.004}},
  volume       = {{5}},
  year         = {{2020}},
}