TY - JOUR
T1 - Pleiotropic Anti-atherosclerotic Effects of PCSK9 InhibitorsFrom Molecular Biology to Clinical Translation
AU - Karagiannis, Angelos D.
AU - Liu, Martin
AU - Toth, Peter P.
AU - Zhao, Shijia
AU - Agrawal, Devendra K.
AU - Libby, Peter
AU - Chatzizisis, Yiannis S.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Purpose of Review: Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors. Recent Findings: PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Summary: Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
AB - Purpose of Review: Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors. Recent Findings: PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Summary: Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
KW - Alirocumab
KW - Anti-atherosclerotic effects
KW - Atherosclerosis
KW - Evolocumab
KW - Inclisiran
KW - PCSK9 inhibitors
KW - Pleiotropic effects
KW - Proprotein convertase subtilisin/kexin 9
UR - http://www.scopus.com/inward/record.url?scp=85043495681&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043495681&partnerID=8YFLogxK
U2 - 10.1007/s11883-018-0718-x
DO - 10.1007/s11883-018-0718-x
M3 - Review article
C2 - 29525934
AN - SCOPUS:85043495681
VL - 20
JO - Current Atherosclerosis Reports
JF - Current Atherosclerosis Reports
SN - 1523-3804
IS - 4
M1 - 20
ER -