{rfName}
SA

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Grant support

grant (CD22/00101) . SF was supported by Comunidad de Madrid grants PEJ-2021-TL/BMD-22441.r grant (CD22/00101) . SF was supported by Comunidad de Madrid grants PEJ-2021-TL/BMD-22441.

Analysis of institutional authors

Villacampa, AliciaAuthorShamoon, LiciaAuthorValencia, InesAuthorDe La Cuesta, FernandoAuthorSánchez-Niño, DoloresAuthorSanchez Perez, Maria IsabelAuthor or co-author of article in journal with external admissions assessment committeeLorenzo, OscarCorresponding AuthorPeiro, ConcepcionCorresponding Author
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Early Access

SARS-CoV-2 S Protein Reduces Cytoprotective Defenses and Promotes Human Endothelial Cell Senescence

Publicated to:Aging and Disease. - 2025-07-05 (), DOI: 10.14336/ad.2024.0405

Authors: Villacampa, Alicia; Shamoon, Licia; Valencia, Ines; Morales, Cristina; Figueiras, Sofia; de la Cuesta, Fernando; Sanchez-Nino, Dolores; Diaz-Araya, Guillermo; Sanchez-Perez, Isabel; Lorenzo, Oscar; Sanchez-Ferrer, Carlos Felix; Peiro, Concepcion

Affiliations

Biomed Res Networking Ctr Diabet & Assoc Metab Dis, Madrid, Spain - Author
IdiPAZ, Vasc Pharmacol & Metab FARMAVASM Grp, Madrid, Spain - Author
IIS Fdn Jimenez Diaz, Lab Diabet & Vasc pathol, Madrid, Spain - Author
IIS Fdn Jimenez Diaz, Nephrol & Hypertens Lab, Madrid, Spain - Author
IIS Hosp Univ La Princesa, Hosp Univ Santa Cristina, Mol Neuroinflammat & Neuronal Plast Res Lab, Madrid, Spain - Author
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Biomarkers & Personalized Approach Canc BioPAC Grp, Area Canc 3, Madrid, Spain - Author
ISCIII, CIBERER, Biomed Res Networking Ctr Rare Dis, Madrid, Spain - Author
UAM, CSIC, Inst Invest Biomed Sols Morreale IIBM, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Biochem, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Med, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Pharmacol, Madrid, Spain - Author
Univ Chile, Fac Chem & Pharmaceut Sci, Dept Pharmacol & Toxicol Chem, Santiago, Chile - Author
Univ Chile, Fac Med, Santiago, Chile - Author
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Abstract

Premature vascular aging and endothelial cell senescence are major risk factors for cardiovascular diseases and atherothrombotic disturbances, which are main complications of both acute and long COVID-19. The S protein of SARS-CoV2, which acts as the receptor binding protein for the viral infection, is able to induce endothelial cells inflammation and it has been found as an isolated element in the circulation and in human tissues reservoirs months after infection. Here, we investigated whether the S protein is able to directly induce endothelial cell senescence and deciphered some of the mechanisms involved. In primary cultures of human umbilical vein endothelial cells (HUVEC), SARS-CoV-2 S protein enhanced in a concentration-dependent manner the cellular content of senescence and DNA damage response markers (senescence-associated- beta galactosidase, gamma H2AX), as well as growth-arrest effectors (p53, p21, p16). In parallel, the S protein reduced the availability of cytoprotective proteins, such as the antiaging protein klotho, Nrf2 or heme oxygenase-1, and caused functional harm by impairing ex vivo endothelialdependent vasorelaxation in murine microvessels. These effects were prevented by the pharmacological inhibition of the NLRP3 inflammasome with MCC950. Furthermore, the supplementation with either recombinant klotho or angiotensin-(1-7), equally protected against the pro-senescence, pro-inflammatory and pro-oxidant action of the S protein. Globally, this study proposes novel mechanisms of disease in the context of COVID-19 and its vascular sequelae and provides pharmacological clues in order to prevent such complications.

Keywords
Angiotensin-(1-7CytoprotectionEndothelial cell senescenceKlothoSars-cov-2 s protein

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Aging and Disease due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 6/74, thus managing to position itself as a Q1 (Primer Cuartil), in the category Geriatrics & Gerontology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-04-28:

  • WoS: 1
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-28:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 7.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 6 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 18.85.
  • The number of mentions on the social network X (formerly Twitter): 41 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Chile.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (VILLACAMPA CALVO, ALICIA) and Last Author (PEIRO VALLEJO, M. CONCEPCION).

the authors responsible for correspondence tasks have been LORENZO GONZALEZ, OSCAR, Sanchez-Ferrer, Carlos Felix and PEIRO VALLEJO, M. CONCEPCION.