Pharmacological clearance of senescent cells reduces inflammation, endothelial damage and cardiac fibrosis in HFpEF
ZSF1-Obese rats had increased immune and endothelial senescent cells in their peripheral blood and myocardium, together with exacerbated systemic inflammation and endothelial damage, compared to control ZSF1-Lean rats. Moreover, increased circulating senescent leucocytes were associated with markers of disease severity in patients with HFpEF. Senescent cell clearance decreased circulating B-type natriuretic peptide levels and attenuated inflammation, vascular remodelling, and cardiac fibrosis. Additionally, it improved renal function and reduced pulmonary oedema. Our findings suggest that senotherapeutics may improve the treatment for HFpEF by attenuating systemic effects of the disease whilst reducing cardiac fibrosis and endothelial rarefaction.
Authors
- António Angélico‐Gonçalves (ORCID: https://orcid.org/0000-0003-2765-1738)
- António S. Barros (ORCID: https://orcid.org/0000-0002-9103-5852)
- Daniela Miranda‐Silva (ORCID: https://orcid.org/0000-0001-8438-3851)
- James L. Kirkland (ORCID: https://orcid.org/0000-0003-1676-4905)
- Nádia Pereira Gonçalves (ORCID: https://orcid.org/0000-0002-5534-958X)
- Reinier A. Boon (ORCID: https://orcid.org/0000-0001-7944-9748)
- Francisco Caramelo (ORCID: https://orcid.org/0000-0002-0015-8604)
- Perpétua Pinto‐do‐Ó (ORCID: https://orcid.org/0000-0002-6477-6030)
- Elsa D. Silva (ORCID: https://orcid.org/0000-0001-5113-7355)
- Tamar Tchkonia (ORCID: https://orcid.org/0000-0003-4623-7145)
- Rio P. Juni (ORCID: https://orcid.org/0000-0002-5850-2869)
- Alexandre Gonçalves (ORCID: https://orcid.org/0000-0001-7822-1856)
- Glória Conceição (ORCID: https://orcid.org/0000-0002-7986-2425)
- Inês Tomé (ORCID: https://orcid.org/0000-0001-8147-1004)
- Adelino Leite‐Moreira (ORCID: https://orcid.org/0000-0001-7808-3596)
- Patrícia R. Pitrez (ORCID: https://orcid.org/0000-0002-3116-0723)
- Susana G. Santos (ORCID: https://orcid.org/0000-0002-8604-2978)
- Pedro Mendes‐Ferreira (ORCID: https://orcid.org/0000-0003-3616-6785)
- Inês Falcão‐Pires (ORCID: https://orcid.org/0000-0003-1937-3782)
- Rui Adão (ORCID: https://orcid.org/0000-0003-2203-436X)
- Vasco Sampaio‐Pinto (ORCID: https://orcid.org/0000-0002-7129-0493)
- João Ribeiro (ORCID: https://orcid.org/0000-0002-7658-4837)
- Lino Ferreira (ORCID: https://orcid.org/0000-0001-8985-9302)
- Diana S. Nascimento (ORCID: https://orcid.org/0000-0001-6402-4245)
- Andreia Silva (ORCID: https://orcid.org/0000-0001-6365-1407)
- Daniel Pereira-Sousa (ORCID: https://orcid.org/0000-0002-2334-4610)
- Carolina Caetano (ORCID: https://orcid.org/0000-0003-0493-7653)
- Francisco Vasques-Nóvoa
Institutions
- Goethe University Frankfurt (DE)
- Mayo Clinic (US)
- Goethe-Institute United Kingdom (GB)
- Universidade do Porto (PT)
- Hospital de São João (PT)
- Escola Superior de Tecnologia da Saúde de Coimbra (PT)
- German Centre for Cardiovascular Research (DE)
- DIPF | Leibniz Institute for Research and Information in Education (DE)
- Amsterdam University Medical Centers (NL)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
- University of Coimbra (PT)
- Vrije Universiteit Amsterdam (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-10-27
- DOI
- https://doi.org/10.1093/cvr/cvaf208
- Citations
- 1
- Primary Topic
- Telomeres, Telomerase, and Senescence
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Noaber Foundation
- European Commission
- Universidade de Santiago de Compostela
- National Institutes of Health
- European Regional Development Fund