Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis.

cardiovascular diseases fibroblasts fibrosis heart failure pericytes

Journal

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

Informations de publication

Date de publication:
02 Apr 2024
Historique:
medline: 2 4 2024
pubmed: 2 4 2024
entrez: 2 4 2024
Statut: aheadofprint

Résumé

Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.

Sections du résumé

BACKGROUND UNASSIGNED
Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown.
METHODS UNASSIGNED
In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts.
RESULTS UNASSIGNED
Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of
CONCLUSIONS UNASSIGNED
Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.

Identifiants

DOI: 10.1161/CIRCRESAHA.123.324183 PMID: 38563133
pubmed: 38563133
doi: 10.1161/CIRCRESAHA.123.324183
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Anita Tamiato (A)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
ORCID: 0000-0002-0022-339X

Lukas S Tombor (LS)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).

Ariane Fischer (A)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
ORCID: 0000-0001-8074-3354

Marion Muhly-Reinholz (M)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).

Leah Rebecca Vanicek (LR)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).

Büşra Nur Toğru (BN)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).

Jessica Neitz (J)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).

Simone Franziska Glaser (SF)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).

Maximilian Merten (M)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).

David Rodriguez Morales (D)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
ORCID: 0000-0002-1819-6991

Jeonghyeon Kwon (J)

Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. (J.K., N.W.).
ORCID: 0009-0000-5818-0110

Stephan Klatt (S)

Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
Institute for Vascular Signalling, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (S.K., I.F.).
ORCID: 0000-0003-0064-3367

Bianca Schumacher (B)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).

Stefan Günther (S)

Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. (S.G.).

Wesley T Abplanalp (WT)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
ORCID: 0000-0001-5996-8997

David John (D)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
ORCID: 0000-0003-3217-5449

Ingrid Fleming (I)

Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
Institute for Vascular Signalling, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (S.K., I.F.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
ORCID: 0000-0003-1881-3635

Nina Wettschureck (N)

Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. (J.K., N.W.).
ORCID: 0000-0001-6858-1460

Stefanie Dimmeler (S)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
ORCID: 0000-0002-1045-2436

Guillermo Luxán (G)

Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Germany. (A.T., L.S.T., A.F., M.M.-R., L.R.V., B.N.T., J.N., S.F.G., M.M., D.R.M., B.S., W.T.A., D.J., S.D., G.L.).
Cardiopulmonary Institute, Goethe University Frankfurt, Germany. (A.T., L.S.T., S.F.G., M.M., S.K., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).
German Center for Cardiovascular Research DZHK, Frankfurt am Main, Germany (A.T., L.S.T., S.F.G., M.M., B.S., S.G., W.T.A., D.J., I.F., N.W., S.D., G.L.).

Classifications MeSH