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

JACC: Basic to Translational Science（2020）

Cited 44|Views80
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Abstract
•Aortic stenosis was less prevalent in carriers of the PCSK9 R46L variant.•Variation at the PCSK9 locus influences LDL-C levels, but not Lp(a).•PCSK9 is produced and secreted by aortic valves.•In vitro, PCSK9 inhibition might lower calcification in aortic valve cells.•PCSK9 inhibition could represent a therapeutic strategy for aortic stenosis.
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Key words
aortic valve interstitial cell,apolipoprotein B,calcific aortic valve stenosis,LDL cholesterol,lipoprotein(a),proprotein convertase subtilisin/kexin type 9
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