@article{10902/37721,
year = {2025},
url = {https://hdl.handle.net/10902/37721},
abstract = {Cardiac fibrosis is a key characteristic of heart failure. CTPR390, an experimental anti-fibrotic inhibitor targeting Hsp90, has shown success in animal models, but remains unexplored in human cardiac models. This study evaluated an engineered cardiac connective tissue (ECCT) model, focusing on changes in the extracellular matrix and fibroblasts. Results showed that CTPR390 prevented architectural changes in TGFb1-activated ECCT, preserving tissue perimeter, collagen fibers alignment while reducing structured areas and degree of collagen structuration. CTPR390 treatment reduced cell area of fibroblasts under tension, without changes in the internal rounded cells devoid of tension. Fibroblast recruitment to tension areas was diminished, showing biomechanical behavior similar to control ECCT. This treatment also lowered the gene and protein expression of key pro-fibrotic markers. Here, advanced biotechnology was employed to detect the detailed structure of tissue fibrosis reduction after administering CTPR390, representing a significant advancement toward clinical application for cardiac fibrosis treatment.},
organization = {This work was partially supported by Agencia Estatal de Investigacio´ n
(AEI/MCI/10.13039/501100011033), Spain. A.V.V. PID2021-125702OB-I00.
Fomento de la transferencia de conocimiento en la Comunidad Auto´ noma
de Cantabria SUBVTC-2023-0006 T. A.L.C. acknowledges support by
the Agencia Estatal de Investigacio´ n Grant PDC2021-120957-I00-NanoIVD
and PDC2022-133345-I00-ProIMAGE funded by MCIN/AEI/10.13039/
501100011033 and by the ‘‘European Union NextGenerationEU/PRTR’’ and
Grant PID2022-137977OB-I00-ProTher funded by MCIN/AEI/ 10.13039/
501100011033. C.S.C. thanks Gipuzkoa Foru Aldundia (Gipuzkoa Fellows program) Grant number 2019-FELL-000018-01/62/2019 for financial support. G.
G. thanks the financial support of ‘‘la Caixa’’ Foundation (ID100010434, fellowship: LCF/BQ/DI20/11780020).},
publisher = {Elsevier},
publisher = {iScience, 2025, 28(8). 113013},
title = {Cardiac fibrosis inhibitor CTPR390 prevents structural and morphological changes in human engineered cardiac connective tissue},
author = {Maestro Lavín, David and Palanca Cuñado, Ana Rosa and Soto Pérez-Cejuela, Helena and Llarena, I. and DeGrave, Alisa Nicole and Guedes, Gabriela and Coelho Conceiçao, André Luliz and Oliveira, Guilherme Henrique de and Mieites, Verónica and Icardo de la Escalera, José Manuel and Sánchez-Cano, Carlos and Conde, Olga M. and Lutz, Susanne and Cortajarena, Aitziber L. and Villar Ramos, Ana Victoria},
}