PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.

Animals Carotid Arteries / metabolism Cell Movement Cell Proliferation Cells, Cultured Male Matrix Metalloproteinases / genetics Mice Mice, Inbred C57BL Myocytes, Smooth Muscle / metabolism Polymorphism, Single Nucleotide Proprotein Convertases / genetics Proto-Oncogene Proteins c-sis / metabolism Rats Rats, Sprague-Dawley Serine Endopeptidases / genetics Transcriptome Vascular Remodeling
atherosclerosis carotid artery injuries endarterectomy extracellular matrix vascular remodeling

Journal

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

Informations de publication

Date de publication:
28 02 2020
Historique:
pubmed: 3 1 2020
medline: 31 10 2020
entrez: 3 1 2020
Statut: ppublish

Résumé

PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. Here, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall. Genetic analyses revealed association of intronic PCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.

Identifiants

DOI: 10.1161/CIRCRESAHA.119.316063 PMID: 31893970
pubmed: 31893970
doi: 10.1161/CIRCRESAHA.119.316063
doi:

Substances chimiques

Proto-Oncogene Proteins c-sis 0
PCSK6 protein, human EC 3.4.21.-
Proprotein Convertases EC 3.4.21.-
Serine Endopeptidases EC 3.4.21.-
Matrix Metalloproteinases EC 3.4.24.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

571-585

Subventions

Organisme : British Heart Foundation
ID : PG 08/008
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Auteurs

Urszula Rykaczewska (U)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Bianca E Suur (BE)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Samuel Röhl (S)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Anton Razuvaev (A)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Mariette Lengquist (M)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Maria Sabater-Lleal (M)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).
Unit of Genomics of Complex Diseases, Institut de Recerca Hospital de Sant Pau (IIB-Sant Pau), Barcelona, Spain (M.S.-L.).

Sander W van der Laan (SW)

Central Diagnostics Laboratory, Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, The Netherlands (S.v.d.L.).

Clint L Miller (CL)

Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville (C.L.M.).
Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (C.L.M., R.C.W., T.Q.).

Robert C Wirka (RC)

Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (C.L.M., R.C.W., T.Q.).

Malin Kronqvist (M)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Maria Gonzalez Diez (M)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).

Mattias Vesterlund (M)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Sweden (M.V., J.L.).

Peter Gillgren (P)

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Department of Vascular Surgery, Södersjukhuset, Stockholm, Sweden (P.G.).

Jacob Odeberg (J)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).
Science for Life Laboratory, Department of Proteomics, School of Chemistry Biotechnology and Health (CBH), KTH, Stockholm, Sweden (J.O.).

Jan H Lindeman (JH)

Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).

Fabrizio Veglia (F)

Centro Cardiologico Monzino, IRCCS, Milan, Italy (F.V., D.B., E.T.).

Steve E Humphries (SE)

Cardiovascular Genetics, Institute Cardiovascular Science, University College of London, Department of Medicine, Rayne Building, United Kingdom (S.E.H.).

Ulf de Faire (U)

Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Sweden (H.d.F.).

Damiano Baldassarre (D)

Centro Cardiologico Monzino, IRCCS, Milan, Italy (F.V., D.B., E.T.).
Department of Medical Biotechnology and Translational Medicine, Università di Milano, Milan, Italy (D.B.).

Elena Tremoli (E)

Centro Cardiologico Monzino, IRCCS, Milan, Italy (F.V., D.B., E.T.).

Janne Lehtiö (J)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, Sweden (M.V., J.L.).

Göran K Hansson (GK)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).

Gabrielle Paulsson-Berne (G)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).

Gerard Pasterkamp (G)

Laboratory of Experimental Cardiology, Division Heart & Lungs, University Medical Center Utrecht, The Netherlands (G.P.).

Thomas Quertermous (T)

Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (C.L.M., R.C.W., T.Q.).

Anders Hamsten (A)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).

Per Eriksson (P)

Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (M.S.-L., M.G.D., G.P.-B., G.K.H., A.H., P.E., J.O.).

Ulf Hedin (U)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

Ljubica Matic (L)

From the Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (U.R., B.E.S., S.R., A.R., M.L., M.K., U.H., L.M.).

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Artères › Artères carotides › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Cellules › Cellules cultivées › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Metalloproteases › Metalloendopeptidases › Matrix metalloproteinases › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes du muscle lisse › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Proprotein convertases › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteur de croissance dérivé des plaquettes › Protéines proto-oncogènes c-sis › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › PCSK6 Is a Key Protease in the Control of...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Remodelage vasculaire › PCSK6 Is a Key Protease in the Control of...