Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 5, Issue 7, Pages 649-661Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2020.05.004
Keywords
aortic valve interstitial cell; apolipoprotein B; calcific aortic valve
Categories
Funding
- European Research Area Network on Cardiovascular Disease (ERA-CVD) Joint Transnational Call 2018 through the current EU Framework Programme for Research and Innovation `Horizon 2020' [PICASSO JTC2018-042]
- Italian Ministry of Health [GR-2018-12366423]
- Fondation de l'IUCPQ
- Fondazione Gigi & Pupa Ferrari ONLUS [FPF-14]
- Pfizer
- Cancer Research UK [14136]
- Medical Research Council [G1000143]
- Assistance Publique-Hopitaux de Paris [NCT00338676, NCT00647088]
- Connect Talent research chair from Region Pays de la Loire
- Nantes Metropole
- German Research Foundation (Excellence Cluster ImmunoSensation)
- Fritz Thyssen Foundation
- Daimler and Benz Foundation
- Fonds de Recherche du Quebec: Sante (FRQS)
- McGill University Health Centre Foundation
- Federation Francaise de Cardiologie
- Fondation Coeur et Recherche
- Inserm Translational Research grant
- Canadian Institutes of Health Research (CIHR)
- Swedish Heart-Lung Foundation [2016-0134, 2016-0315]
- Swedish Research Council [2017-02554]
- European Research Council [ERC-STG-2015-679242]
- Crafoord Foundation
- Scania county, governmental funding of clinical research within the Swedish National Health Service
- Swedish Research Council (Linnaeus grant) [349-2006-237]
- Swedish Research Council (Strategic Research Area Exodiab) [2009-1039]
- Swedish Foundation for Strategic Research [IRC15-0067]
- National Institutes of Health/National Heart, Lung, and Blood Institute [R01 HL128550]
- Servier
- Ionis Pharmaceuticals
- Medtronic
- Abbott/St. Jude
- Edwards Lifesciences
- Merck
- Skane University Hospital
- MRC [MC_UU_00006/1, MC_UU_12015/1] Funding Source: UKRI
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The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A men-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. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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