Distinct role of mitochondrial function and protein kinase C in intimal and medial calcification

drug repurposing matrix mineralization mitochondrial function protein kinase C vascular calcification vascular smooth muscle cells

Journal

Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388

Informations de publication

Date de publication:
2022
Historique:
received: 01 06 2022
accepted: 15 08 2022
entrez: 7 10 2022
pubmed: 8 10 2022
medline: 8 10 2022
Statut: epublish

Résumé

Vascular calcification (VC) is a major risk factor for cardiovascular morbidity and mortality. Depending on the location of mineral deposition within the arterial wall, VC is classified as intimal and medial calcification. Using Human coronary artery SMCs were cultured in osteogenic medium (OM) or high calcium phosphate medium (CaP) to induce a mineralized extracellular matrix. OM induces osteoblast-like differentiation of SMCs-a key process in intimal calcification during atherosclerotic plaque remodeling. CaP mimics hyperphosphatemia, associated with chronic kidney disease-a risk factor for medial calcification. Transcriptomic analysis revealed distinct gene expression profiles of OM and CaP-calcifying SMCs. OM and CaP-treated SMCs shared 107 differentially regulated genes related to SMC contraction and metabolism. Real-time extracellular efflux analysis demonstrated decreased mitochondrial respiration and glycolysis in CaP-treated SMCs compared to increased mitochondrial respiration without altered glycolysis in OM-treated SMCs. Subsequent kinome and Our direct comparison results of two

Identifiants

pubmed: 36204585
doi: 10.3389/fcvm.2022.959457
pmc: PMC9530266
doi:

Types de publication

Journal Article

Langues

eng

Pagination

959457

Informations de copyright

Copyright © 2022 Heuschkel, Babler, Heyn, van der Vorst, Steenman, Gesper, Kappel, Magne, Gouëffic, Kramann, Jahnen-Dechent, Marx, Quillard and Goettsch.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JE declared a shared affiliation with one of the author RK to the handling editor at the time of review.

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Auteurs

Marina A Heuschkel (MA)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Anne Babler (A)

Institute of Experimental Medicine and Systems Biology, University Hospital, RWTH Aachen, Aachen, Germany.

Jonas Heyn (J)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Emiel P C van der Vorst (EPC)

Interdisciplinary Center for Clinical Research, Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany.
Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, Netherlands.
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.

Marja Steenman (M)

L'institut Du Thorax, Inserm UMR 1087, CNRS, INSERM, France and Nantes Université, Nantes, France.

Maren Gesper (M)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Ben A Kappel (BA)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

David Magne (D)

ICBMS UMR CNRS 5246, Université Claude Bernard Lyon 1, Villeurbanne, France.

Yann Gouëffic (Y)

Department of Vascular Surgery, Vascular Center, Groupe Hospitalier Paris Saint-Joseph, Paris, France.

Rafael Kramann (R)

Institute of Experimental Medicine and Systems Biology, University Hospital, RWTH Aachen, Aachen, Germany.
Department of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany.
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, Netherlands.

Willi Jahnen-Dechent (W)

Biointerface Laboratory, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.

Nikolaus Marx (N)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Thibaut Quillard (T)

L'institut Du Thorax, Inserm UMR 1087, CNRS, INSERM, France and Nantes Université, Nantes, France.
PHY-OS Laboratory, INSERM UMR 1238, Nantes University of Medicine, Nantes, France.

Claudia Goettsch (C)

Department of Internal Medicine I-Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Classifications MeSH