Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis.

anti-PCSK9 oxidative stress platelets proprotein convertase subtilisin/kexin type 9 (PCSK9) thrombosis

Journal

Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981

Informations de publication

Date de publication:
16 Mar 2022
Historique:
received: 24 02 2022
revised: 11 03 2022
accepted: 15 03 2022
entrez: 25 3 2022
pubmed: 26 3 2022
medline: 26 3 2022
Statut: epublish

Résumé

Proprotein convertase subtilisin/kexin type 9 (PCSK9), mainly secreted in the liver, is a key regulator of cholesterol homeostasis inducing LDL receptors' degradation. Beyond lipid metabolism, PCSK9 is involved in the development of atherosclerosis, promoting plaque formation in mice and human, impairing the integrity of endothelial monolayer and promoting the events that induce atherosclerosis disease progression. In addition, the PCSK9 ancillary role in the atherothrombosis process is widely debated. Indeed, recent evidence showed a regulatory effect of PCSK9 on redox system and platelet activation. In particular, the role of PCSK9 in the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2) system, of MAP-kinase cascades and of CD36 and LOX-1 downstream pathways, suggests that PCSK9 may be a significant cofactor in atherothrombosis development. This evidence suggests that the serum levels of PCSK9 could represent a new biomarker for the occurrence of cardiovascular events. Finally, other evidence showed that PCSK9 inhibitors, a novel pharmacological tool introduced in clinical practice in recent years, counteracted these phenomena. In this review, we summarize the evidence concerning the role of PCSK9 in promoting oxidative-stress-related atherothrombotic process.

Identifiants

pubmed: 35326219
pii: antiox11030569
doi: 10.3390/antiox11030569
pmc: PMC8945358
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

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Auteurs

Vittoria Cammisotto (V)

Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Department of General Surgery and Surgical Speciality Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy.

Francesco Baratta (F)

Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.

Paola G Simeone (PG)

Department of Medicine and Aging, and Center for Advanced Studies and Technology (CAST), "G. D'Annunzio" University Foundation, 66100 Chieti, Italy.

Cristina Barale (C)

Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy.

Enrico Lupia (E)

Department of Medical Sciences, University of Turin, 10126 Turin, Italy.

Gioacchino Galardo (G)

Department of General Surgery and Surgical Speciality Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy.

Francesca Santilli (F)

Department of Medicine and Aging, and Center for Advanced Studies and Technology (CAST), "G. D'Annunzio" University Foundation, 66100 Chieti, Italy.

Isabella Russo (I)

Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy.

Pasquale Pignatelli (P)

Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Mediterranea Cardiocentro, 80133 Napoli, Italy.

Classifications MeSH