Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms.

Animals Mice Cholesterol Lipoproteins, LDL / metabolism Macrophage Activation NF-kappa B Proprotein Convertase 9 / genetics Receptors, LDL / genetics Serine Endopeptidases / genetics Subtilisins
graft occlusion, vascular inflammation macrophage activation receptors, LDL systems biology

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
11 11 2022
Historique:
pubmed: 21 10 2022
medline: 15 11 2022
entrez: 20 10 2022
Statut: ppublish

Résumé

Activated macrophages contribute to the pathogenesis of vascular disease. Vein graft failure is a major clinical problem with limited therapeutic options. PCSK9 (proprotein convertase subtilisin/kexin 9) increases low-density lipoprotein (LDL)-cholesterol levels via LDL receptor (LDLR) degradation. The role of PCSK9 in macrophage activation and vein graft failure is largely unknown, especially through LDLR-independent mechanisms. This study aimed to explore a novel mechanism of macrophage activation and vein graft disease induced by circulating PCSK9 in an LDLR-independent fashion. We used In Circulating PCSK9 induces macrophage activation and vein graft lesion development via LDLR-independent mechanisms. PCSK9 may be a potential target for pharmacologic treatment for this unmet medical need.

Sections du résumé

BACKGROUND
Activated macrophages contribute to the pathogenesis of vascular disease. Vein graft failure is a major clinical problem with limited therapeutic options. PCSK9 (proprotein convertase subtilisin/kexin 9) increases low-density lipoprotein (LDL)-cholesterol levels via LDL receptor (LDLR) degradation. The role of PCSK9 in macrophage activation and vein graft failure is largely unknown, especially through LDLR-independent mechanisms. This study aimed to explore a novel mechanism of macrophage activation and vein graft disease induced by circulating PCSK9 in an LDLR-independent fashion.
METHODS
We used
RESULTS
In
CONCLUSIONS
Circulating PCSK9 induces macrophage activation and vein graft lesion development via LDLR-independent mechanisms. PCSK9 may be a potential target for pharmacologic treatment for this unmet medical need.

Identifiants

DOI: 10.1161/CIRCRESAHA.121.320056 PMID: 36263780 PMC: PMC9973449
pubmed: 36263780
doi: 10.1161/CIRCRESAHA.121.320056
pmc: PMC9973449
doi:

Substances chimiques

Cholesterol 97C5T2UQ7J
Lipoproteins, LDL 0
NF-kappa B 0
Pcsk9 protein, mouse EC 3.4.21.-
Proprotein Convertase 9 EC 3.4.21.-
Receptors, LDL 0
Serine Endopeptidases EC 3.4.21.-
Subtilisins EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

873-889

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL126901
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149302
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136431
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147095
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141917
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Shunsuke Katsuki (S)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
ORCID: 0000-0001-7851-216X

Prabhash K Jha (P)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).

Adrien Lupieri (A)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
ORCID: 0000-0002-9245-0169

Toshiaki Nakano (T)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
ORCID: 0000-0001-9235-5615

Livia S A Passos (LSA)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
ORCID: 0000-0001-9888-6206

Maximillian A Rogers (MA)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).

Dakota Becker-Greene (D)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).

Thanh-Dat Le (TD)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).

Julius L Decano (JL)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
ORCID: 0000-0003-0388-3585

Lang Ho Lee (L)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
ORCID: 0000-0002-9684-160X

Gabriel C Guimaraes (GC)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).

Ilyes Abdelhamid (I)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Channing Division of Network Medicine (I.A., A.H., A.S., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Arda Halu (A)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Channing Division of Network Medicine (I.A., A.H., A.S., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-6217-790X

Alessandro Muscoloni (A)

The Biomedical Cybernetics Group, Biotechnology Center, Center for Molecular and Cellular Bioengineering, Center for Systems Biology Dresden, Cluster of Excellence Physics of Life, Department of Physics, Technical University Dresden, Dresden, Germany (A.M., C.V.C).
Center for Complex Network Intelligence at the Tsinghua Laboratory of Brain and Intelligence, Department of Bioengineering, Tsinghua University, Beijing, China (A.M., C.V.C.).

Carlo V Cannistraci (C)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Center for Complex Network Intelligence at the Tsinghua Laboratory of Brain and Intelligence, Department of Bioengineering, Tsinghua University, Beijing, China (A.M., C.V.C.).

Hideyuki Higashi (H)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).

Hengmin Zhang (H)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).

Amélie Vromman (A)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).

Peter Libby (P)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
ORCID: 0000-0002-1502-502X

C Keith Ozaki (C)

Center for Complex Network Intelligence at the Tsinghua Laboratory of Brain and Intelligence, Department of Bioengineering, Tsinghua University, Beijing, China (A.M., C.V.C.).
ORCID: 0000-0001-9906-6218

Amitabh Sharma (A)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Channing Division of Network Medicine (I.A., A.H., A.S., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Sasha A Singh (SA)

The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
ORCID: 0000-0003-0929-3164

Elena Aikawa (E)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
ORCID: 0000-0001-7835-2135

Masanori Aikawa (M)

The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
The Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Channing Division of Network Medicine (I.A., A.H., A.S., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-9275-2079

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Lipoprotéines › Lipoprotéines LDL › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Activation des macrophages › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Proprotéine convertase 9 › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux lipoprotéines › Récepteurs aux lipoprotéines LDL › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Proprotein Convertase Subtilisin/Kexin 9...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Subtilisines › Proprotein Convertase Subtilisin/Kexin 9...