TY - JOUR
T1 - Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis
AU - Perrot, Nicolas
AU - Valerio, Vincenza
AU - Moschetta, Donato
AU - Boekholdt, S. Matthijs
AU - Dina, Christian
AU - Chen, Hao Yu
AU - Abner, Erik
AU - Martinsson, Andreas
AU - Manikpurage, Hasanga D.
AU - Rigade, Sidwell
AU - Capoulade, Romain
AU - Mass, Elvira
AU - Clavel, Marie Annick
AU - Le Tourneau, Thierry
AU - Messika-Zeitoun, David
AU - Wareham, Nicholas J.
AU - Engert, James C.
AU - Polvani, Gianluca
AU - Pibarot, Philippe
AU - Esko, Tõnu
AU - Smith, J. Gustav
AU - Mathieu, Patrick
AU - Thanassoulis, George
AU - Schott, Jean Jacques
AU - Bossé, Yohan
AU - Camera, Marina
AU - Thériault, Sébastien
AU - Poggio, Paolo
AU - Arsenault, Benoit J.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - aortic valve interstitial cell
KW - apolipoprotein B
KW - calcific aortic valve stenosis
KW - LDL cholesterol
KW - lipoprotein(a)
KW - proprotein convertase subtilisin/kexin type 9
U2 - 10.1016/j.jacbts.2020.05.004
DO - 10.1016/j.jacbts.2020.05.004
M3 - Article
C2 - 32760854
AN - SCOPUS:85087405073
SN - 2452-302X
VL - 5
SP - 649
EP - 661
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 7
ER -