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 Pîbarot, Tõnu Esko, J. G. Smith, Patrick Mathieu, George Thanassoulis, Jean‐Jacques Schott, Yohan Bossé, Marina Camera, Sébastien Thériault, Paolo Poggio, Benoît J. Arsenault
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.