Proprotein convertase subtilisin kexin type 9 inhibitors reduce platelet activation modulating ox-LDL pathways

Autor: Vittoria Cammisotto, Daniele Pastori, Francesco Baratta, Roberto Scicali, Salvatore Piro, Roberto Carnevale, Francesco Violi, Francesco Purrello, Maria Del Ben, Isabella Russo, Simona Bartimoccia, Antonino Di Pino, Cristina Barale, Laura D'Erasmo, Cristina Nocella, Valentina Castellani, Marcello Arca, Nicholas Cocomello, Pasquale Pignatelli
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Thromboxane
Familial hypercholesterolemia
NOX2
Ox-LDL
PCSK9
Platelets
030204 cardiovascular system & hematology
0302 clinical medicine
030212 general & internal medicine
Biology (General)
Spectroscopy
Chemistry
Anticholesteremic Agents
PCSK9 Inhibitors
Antibodies
Monoclonal
General Medicine
Middle Aged
Computer Science Applications
Lipoproteins
LDL
Italy
NADPH Oxidase 2
Kexin
Female
lipids (amino acids
peptides
and proteins)
Proprotein Convertase 9
medicine.drug
Adult
medicine.medical_specialty
Statin
medicine.drug_class
QH301-705.5
Antibodies
Monoclonal
Humanized
Catalysis
Article
Inorganic Chemistry
Hyperlipoproteinemia Type II
03 medical and health sciences
Ezetimibe
Internal medicine
medicine
Humans
Platelet activation
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Aged
Organic Chemistry
Cholesterol
LDL
medicine.disease
Proprotein convertase
Platelet Activation
Endocrinology
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 22, Iss 7193, p 7193 (2021)
Volume 22
Issue 13
Popis: Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p <
0.001). The decrease of TxB2 correlates with that of ox-LDL, while ox-LDL reduction correlated with PCSK9 and sNOX2-dp delta. In vitro study demonstrated that wPLTs resuspended in plasma from HeFH after PCSK9i treatment induced lower PA and sNOX2-dp release than those obtained using plasma before PCSK9i treatment. This reduction was vanished by adding ox-LDL. ox-LDL-induced PA was blunted by CD36, LOX1, and NOX2 inhibition. Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients.
Databáze: OpenAIRE
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