Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis
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, impa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/3/569 |
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| author | Vittoria Cammisotto Francesco Baratta Paola G. Simeone Cristina Barale Enrico Lupia Gioacchino Galardo Francesca Santilli Isabella Russo Pasquale Pignatelli |
| author_facet | Vittoria Cammisotto Francesco Baratta Paola G. Simeone Cristina Barale Enrico Lupia Gioacchino Galardo Francesca Santilli Isabella Russo Pasquale Pignatelli |
| author_sort | Vittoria Cammisotto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:10:29Z |
| format | Article |
| id | doaj.art-459481b4ab01406fb8e213de0805574c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T20:10:29Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-459481b4ab01406fb8e213de0805574c2023-11-24T00:18:55ZengMDPI AGAntioxidants2076-39212022-03-0111356910.3390/antiox11030569Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and ThrombosisVittoria Cammisotto0Francesco Baratta1Paola G. Simeone2Cristina Barale3Enrico Lupia4Gioacchino Galardo5Francesca Santilli6Isabella Russo7Pasquale Pignatelli8Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Medicine and Aging, and Center for Advanced Studies and Technology (CAST), “G. D’Annunzio” University Foundation, 66100 Chieti, ItalyDepartment of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of General Surgery and Surgical Speciality Paride Stefanini, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Medicine and Aging, and Center for Advanced Studies and Technology (CAST), “G. D’Annunzio” University Foundation, 66100 Chieti, ItalyDepartment of Clinical and Biological Sciences, University of Turin, 10043 Turin, ItalyDepartment of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyProprotein 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.https://www.mdpi.com/2076-3921/11/3/569proprotein convertase subtilisin/kexin type 9 (PCSK9)plateletsthrombosisanti-PCSK9oxidative stress |
| spellingShingle | Vittoria Cammisotto Francesco Baratta Paola G. Simeone Cristina Barale Enrico Lupia Gioacchino Galardo Francesca Santilli Isabella Russo Pasquale Pignatelli Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis Antioxidants proprotein convertase subtilisin/kexin type 9 (PCSK9) platelets thrombosis anti-PCSK9 oxidative stress |
| title | Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis |
| title_full | Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis |
| title_fullStr | Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis |
| title_full_unstemmed | Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis |
| title_short | Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Beyond Lipids: The Role in Oxidative Stress and Thrombosis |
| title_sort | proprotein convertase subtilisin kexin type 9 pcsk9 beyond lipids the role in oxidative stress and thrombosis |
| topic | proprotein convertase subtilisin/kexin type 9 (PCSK9) platelets thrombosis anti-PCSK9 oxidative stress |
| url | https://www.mdpi.com/2076-3921/11/3/569 |
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