Cardiac Microvascular Endothelial Cells in Pressure Overload-Induced Heart Disease.

ADAMTS Proteins / genetics Aged Animals Aorta Aortic Valve Stenosis / genetics Collagen Type I / genetics Collagen Type I, alpha 1 Chain Constriction, Pathologic Coronary Vessels / metabolism Disease Models, Animal Endothelial Cells / metabolism Extracellular Matrix Proteins / genetics Fatty Acids / metabolism Female Gene Expression Profiling Heart Atria / metabolism Heart Valve Prosthesis Implantation Heart Ventricles / metabolism Humans Male Mice Mice, Transgenic Microvascular Density Microvessels / metabolism Procollagen / metabolism Proline / metabolism Pyrophosphatases / genetics Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, RNA Thrombospondins / genetics
constriction endothelial cells heart failure mice phenotype

Journal

Circulation. Heart failure
ISSN: 1941-3297
Titre abrégé: Circ Heart Fail
Pays: United States
ID NLM: 101479941

Informations de publication

Date de publication:
01 2021
Historique:
entrez: 19 1 2021
pubmed: 20 1 2021
medline: 27 7 2021
Statut: ppublish

Résumé

Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation of cardiac MiVEC to pressure overload in mice and patients with aortic stenosis (AS). In In mice, transverse aortic constriction induced progressive systolic dysfunction, fibrosis, and reduced microvascular density. After 10 weeks, 25 genes predominantly involved in matrix-regulation were >2-fold upregulated in isolated MiVEC. Increased transcript levels of Pressure overload induces major transcriptional and metabolic adaptations in cardiac MiVEC resulting in excess interstitial fibrosis and impaired angiogenesis. Molecular rewiring of MiVEC is worse in women, compromises functional status, and identifies novel targets for intervention.

Sections du résumé

BACKGROUND
Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation of cardiac MiVEC to pressure overload in mice and patients with aortic stenosis (AS).
METHODS
In
RESULTS
In mice, transverse aortic constriction induced progressive systolic dysfunction, fibrosis, and reduced microvascular density. After 10 weeks, 25 genes predominantly involved in matrix-regulation were >2-fold upregulated in isolated MiVEC. Increased transcript levels of
CONCLUSIONS
Pressure overload induces major transcriptional and metabolic adaptations in cardiac MiVEC resulting in excess interstitial fibrosis and impaired angiogenesis. Molecular rewiring of MiVEC is worse in women, compromises functional status, and identifies novel targets for intervention.

Identifiants

DOI: 10.1161/CIRCHEARTFAILURE.120.006979 PMID: 33464950
pubmed: 33464950
doi: 10.1161/CIRCHEARTFAILURE.120.006979
doi:

Substances chimiques

Adamtsl2 protein, mouse 0
Collagen Type I 0
Collagen Type I, alpha 1 Chain 0
Extracellular Matrix Proteins 0
Fatty Acids 0
Procollagen 0
Thrombospondins 0
thrombospondin 4 0
Proline 9DLQ4CIU6V
ADAMTS Proteins EC 3.4.24.-
CILP protein, mouse EC 3.6.1.-
Pyrophosphatases EC 3.6.1.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e006979

Auteurs

Sander Trenson (S)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Hadewich Hermans (H)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Sander Craps (S)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Peter Pokreisz (P)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Pauline de Zeeuw (P)

Department of Oncology, Laboratory of Angiogenesis and Vascular Metabolism (P.d.Z., P.C.), KU Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium (P.d.Z., P.C.).

Jore Van Wauwe (J)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Hilde Gillijns (H)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Denise Veltman (D)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Fangfei Wei (F)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Ellen Caluwé (E)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Rik Gijsbers (R)

Department of Pharmacological and Pharmaceutical Sciences, Laboratory for Viral Vector Technology and Gene therapy and Leuven Viral Vector Core (R.G.), KU Leuven, Belgium.

Pieter Baatsen (P)

VIB-University of Leuven Center for Brain and Disease Research, Leuven, Belgium (P.B.).

Jan A Staessen (JA)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Bart Ghesquiere (B)

Metabolomics Expertise Center, Center for Cancer biology, VIB, Leuven, Belgium (B.G.).

Peter Carmeliet (P)

Department of Oncology, Laboratory of Angiogenesis and Vascular Metabolism (P.d.Z., P.C.), KU Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium (P.d.Z., P.C.).

Filip Rega (F)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Bart Meuris (B)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Bart Meyns (B)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Wouter Oosterlinck (W)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Jürgen Duchenne (J)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Kaatje Goetschalckx (K)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Jens-Uwe Voigt (JU)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Marie-Christine Herregods (MC)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Paul Herijgers (P)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Aernout Luttun (A)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

Stefan Janssens (S)

Department of Cardiovascular Sciences (S.T., H.H., S.C., P.P., J.V.W., H.G., D.V., F.W., E.C., J.A.S., F.R., B. Meuris, B. Meyns, W.O., J.D., K.G., J.-U.V., M.-C.H., P.H., A.L., S.J.), KU Leuven, Belgium.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Protéines ADAMTS › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Artères › Aorte › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Obstacle à l'éjection ventriculaire › Sténose aortique › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type I › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Structures macromoléculaires › Chaine alpha-1 du collagène de type I › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Sténose pathologique › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Veines › Vaisseaux coronaires › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Lipides › Acides gras › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Atrium du coeur › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie thoracique › Procédures de chirurgie cardiaque › Implantation de valve prothétique cardiaque › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Ventricules cardiaques › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Densité microvasculaire › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Microvaisseaux › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Procollagène › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés cycliques › Imino-acides › Proline › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › Pyrophosphatases › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Techniques d'amplification d'acides nucléiques › Réaction de polymérisation en chaîne › RT-PCR › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Cardiac Microvascular Endothelial Cells in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Thrombospondines › Cardiac Microvascular Endothelial Cells in...