RT Journal Article
T1 Ccn2 deletion reduces cardiac dysfunction, oxidative markers, and fibrosis induced by doxorubicin administration in mice
A1 Tejera-Muñoz, Antonio
A1 Cortés, Marcelino
A1 Rodriguez-Rodriguez, Alianet
A1 Tejedor-Santamaria, Lucia
A1 Marchant, Vanessa
A1 Rayego-Mateos, Sandra
A1 Gimeno Longas, María José
A1 Leask, Andrew
A1 Nguyen, Tri Q
A1 Martín, María
A1 Tuñón, José
A1 Rodriguez, Isabel
A1 Ruiz-Ortega, Marta
A1 Rodrigues Díez, Raúl
AB Cellular Communication Network Factor 2 (CCN2) is a matricellular protein implicated in cell communication and microenvironmental signaling. Overexpression of CCN2 has been documented in various cardiovascular pathologies, wherein it may exert either deleterious or protective effects depending on the pathological context, thereby suggesting that its role in the cardiovascular system is not yet fully elucidated. In this study, we aimed to investigate the effects of Ccn2 gene deletion on the progression of acute cardiac injury induced by doxorubicin (DOX), a widely utilized chemotherapeutic agent. To this end, we employed conditional knockout (KO) mice for the Ccn2 gene (CCN2-KO), which were administered DOX and compared to DOX-treated wild-type (WT) control mice. Our findings demonstrated that the ablation of CCN2 ameliorated DOX-induced cardiac dysfunction, as evidenced by improvements in ejection fraction (EF) and fractional shortening (FS) of the left ventricle. Furthermore, DOX-treated CCN2-KO mice exhibited a significant reduction in the gene expression and activation of oxidative stress markers (Hmox1 and Nfe2l2/NRF2) relative to DOX-treated WT controls. Additionally, the deletion of Ccn2 markedly attenuated DOX-induced cardiac fibrosis. Collectively, these results suggest that CCN2 plays a pivotal role in the pathogenesis of DOX-mediated cardiotoxicity by modulating oxidative stress and fibrotic pathways. These findings provide a novel avenue for future investigations to explore the therapeutic potential of targeting CCN2 in the prevention of DOX-induced cardiac dysfunction.
PB MPDI
SN 1422-0067
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/134095
UL https://hdl.handle.net/20.500.14352/134095
LA eng
NO Tejera-Muñoz, A., Cortés, M., Rodriguez-Rodriguez, A., Tejedor-Santamaria, L., Marchant, V., Rayego-Mateos, S., Gimeno-Longas, M. J., Leask, A., Nguyen, T. Q., Martín, M., Tuñón, J., Rodríguez, I., Ruiz-Ortega, M., & Rodrigues-Díez, R. R. (2024). Ccn2 Deletion Reduces Cardiac Dysfunction, Oxidative Markers, and Fibrosis Induced by Doxorubicin Administration in Mice. International Journal of Molecular Sciences, 25(17), 9617. https://doi.org/10.3390/ijms25179617
NO Sociedad Española de Cardiología (SEC) grant to MRO
NO Sociedad Española de Atherosclerosis (SEA) grant to RRRD
NO PI20/00140 and PI23/00394/Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union
NO RICORS2040; RD21/0005/0002/Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union
NO INNOREN P2022/BMD-7221/Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union
DS Docta Complutense
RD 8 abr 2026