Targeting Filamin A Reduces Macrophage Activity and Atherosclerosis.

Animals Atherosclerosis / genetics Cells, Cultured Filamins / antagonists & inhibitors Gene Targeting / methods Humans Macrophage Activation / physiology Macrophages / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout
cytoskeleton endarterectomy lipids models, animal

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
02 07 2019
Historique:
pubmed: 25 4 2019
medline: 31 3 2020
entrez: 25 4 2019
Statut: ppublish

Résumé

The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored. We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.

Sections du résumé

BACKGROUND
The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.
METHODS
We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna
RESULTS
We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna
CONCLUSIONS
Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.119.039697 PMID: 31014088
pubmed: 31014088
doi: 10.1161/CIRCULATIONAHA.119.039697
doi:

Substances chimiques

Filamins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

67-79

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Auteurs

Sashidar Bandaru (S)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Chandu Ala (C)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Reza Salimi (R)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Murali K Akula (MK)

Sahlgrenska Cancer Center, Sahlgrenska Academy (M.K.A., J.K., M.O.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Matias Ekstrand (M)

Department of Molecular and Clinical Medicine, Institute of Medicine (M.E., G.B., M.L., J.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Sravani Devarakonda (S)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Joakim Karlsson (J)

Sahlgrenska Cancer Center, Sahlgrenska Academy (M.K.A., J.K., M.O.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Surgery, Institute of Clinical Sciences (J.K.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Jimmy Van den Eynden (J)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Human Structure and Repair, Anatomy and Embryology Unit, Ghent University, Belgium (J.V.d.E.).

Göran Bergström (G)

Department of Molecular and Clinical Medicine, Institute of Medicine (M.E., G.B., M.L., J.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Göteborg, Sweden (G.B.).

Erik Larsson (E)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Max Levin (M)

Department of Molecular and Clinical Medicine, Institute of Medicine (M.E., G.B., M.L., J.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Jan Borén (J)

Department of Molecular and Clinical Medicine, Institute of Medicine (M.E., G.B., M.L., J.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.

Martin O Bergo (MO)

Sahlgrenska Cancer Center, Sahlgrenska Academy (M.K.A., J.K., M.O.B.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden (M.O.B.).

Levent M Akyürek (LM)

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine (S.B., C.A., R.S., S.D., J.V.d.E., E.L., L.M.A.), Sahlgrenska Academy, University of Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Pathology and Cytology, Göteborg, Sweden (L.M.A.).

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Artériopathies oblitérantes › Artériosclérose › Athérosclérose › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Cellules › Cellules cultivées › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Filamines › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Activation des macrophages › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Targeting Filamin A Reduces Macrophage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Targeting Filamin A Reduces Macrophage...