Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development: Role of MicroRNA-125b.

Angiotensin II / drug effects Animals Aortic Aneurysm, Abdominal / genetics Apoptosis Cells, Cultured Chelating Agents / pharmacology Copper / metabolism Copper Transport Proteins / metabolism Copper-Transporting ATPases / genetics Disease Models, Animal Down-Regulation Female Humans Inflammation / genetics Male Mice, Inbred C57BL Mice, Transgenic MicroRNAs / physiology Molecular Chaperones / metabolism Molybdenum / pharmacology Muscle, Smooth, Vascular / cytology Up-Regulation
angiotensin II aortic aneurysm copper elastin micronutrient

Journal

Arteriosclerosis, thrombosis, and vascular biology
ISSN: 1524-4636
Titre abrégé: Arterioscler Thromb Vasc Biol
Pays: United States
ID NLM: 9505803

Informations de publication

Date de publication:
11 2019
Historique:
pubmed: 27 9 2019
medline: 9 4 2020
entrez: 27 9 2019
Statut: ppublish

Résumé

Copper (Cu) is essential micronutrient, and its dysregulation is implicated in aortic aneurysm (AA) development. The Cu exporter ATP7A (copper-transporting P-type ATPase/Menkes ATPase) delivers Cu via the Cu chaperone Atox1 (antioxidant 1) to secretory Cu enzymes, such as lysyl oxidase, and excludes excess Cu. Lysyl oxidase is shown to protect against AA formation. However, the role and mechanism of ATP7A in AA pathogenesis remain unknown. Approach and Results: Here, we show that Cu chelator markedly inhibited Ang II (angiotensin II)-induced abdominal AA (AAA) in which ATP7A expression was markedly downregulated. Transgenic ATP7A overexpression prevented Ang II-induced AAA formation. Conversely, Cu transport dysfunctional ATP7A ATP7A downregulation/dysfunction promotes AAA formation via upregulating miR-125b, which augments proinflammatory signaling in a Cu-dependent manner. Thus, ATP7A is a potential therapeutic target for inflammatory vascular disease.

Identifiants

DOI: 10.1161/ATVBAHA.119.313374 PMID: 31554420 PMC: PMC6857803
pubmed: 31554420
doi: 10.1161/ATVBAHA.119.313374
pmc: PMC6857803
mid: NIHMS1540174
doi:

Substances chimiques

Atox1 protein, mouse 0
Atp7a protein, mouse 0
Chelating Agents 0
Copper Transport Proteins 0
MIRN125 microRNA, human 0
MicroRNAs 0
Mirn125 microRNA, mouse 0
Molecular Chaperones 0
Angiotensin II 11128-99-7
Copper 789U1901C5
Molybdenum 81AH48963U
tetrathiomolybdate 91U3TGV99T
ATP7A protein, human EC 7.2.2.8
Copper-Transporting ATPases EC 7.2.2.8

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2320-2337

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL126949
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142097
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135584
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147550
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070029
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133613
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139562
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL116976
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134354
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL070187
Pays : United States
Organisme : BLRD VA
ID : I01 BX001232
Pays : United States

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Auteurs

Varadarajan Sudhahar (V)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.
Charlie Norwood Veterans Affairs Medical Center, Augusta, GA (V.S., S.L., T.F.).

Archita Das (A)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.

Tetsuo Horimatsu (T)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Medicine (Cardiology) (T.H., D.A., N.L.W., H.W.K., M.U.-F.), Medical College of Georgia at Augusta University, GA.

Dipankar Ash (D)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Medicine (Cardiology) (T.H., D.A., N.L.W., H.W.K., M.U.-F.), Medical College of Georgia at Augusta University, GA.

Silvia Leanhart (S)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Charlie Norwood Veterans Affairs Medical Center, Augusta, GA (V.S., S.L., T.F.).

Olga Antipova (O)

X-ray Science Division, Argonne National Laboratory, IL (O.A., S.V.).

Stefan Vogt (S)

X-ray Science Division, Argonne National Laboratory, IL (O.A., S.V.).

Bhupesh Singla (B)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.

Gabor Csanyi (G)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.

Joseph White (J)

Department of Pathology (J.W.), Medical College of Georgia at Augusta University, GA.

Jack H Kaplan (JH)

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago (J.H.K.).

David Fulton (D)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.

Neal L Weintraub (NL)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Medicine (Cardiology) (T.H., D.A., N.L.W., H.W.K., M.U.-F.), Medical College of Georgia at Augusta University, GA.

Ha Won Kim (HW)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Medicine (Cardiology) (T.H., D.A., N.L.W., H.W.K., M.U.-F.), Medical College of Georgia at Augusta University, GA.

Masuko Ushio-Fukai (M)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Medicine (Cardiology) (T.H., D.A., N.L.W., H.W.K., M.U.-F.), Medical College of Georgia at Augusta University, GA.

Tohru Fukai (T)

From the Vascular Biology Center (V.S., A.D., T.H., D.A., S.L., B.S., G.C., D.F., N.L.W., H.W.K., M.U.-F., T.F.), Medical College of Georgia at Augusta University, GA.
Department of Pharmacology and Toxicology (V.S., A.D., B.S., G.C., D.F., T.F.), Medical College of Georgia at Augusta University, GA.
Charlie Norwood Veterans Affairs Medical Center, Augusta, GA (V.S., S.L., T.F.).

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Angiotensines › Angiotensine-II › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Eucaryotes › Animaux › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Maladies de l'aorte › Anévrysme de l'aorte › Anévrysme de l'aorte abdominale › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Cellules › Cellules cultivées › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents séquestrants › Chélateurs › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Cuivre › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs de cations › Protéines de transport du cuivre › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › P-type ATPases › Copper-transporting ATPases › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Chaperons moléculaires › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Molybdène › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Tissus › Muscles › Muscles lisses › Muscles lisses vasculaires › Copper Transporter ATP7A (Copper-Transporting...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Copper Transporter ATP7A (Copper-Transporting...