Journal Article

PUBDB-2025-04941

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cardiac fibrosis inhibitor CTPR390 prevents structural and morphological changes in human engineered cardiac connective tissue

Maestro, D.Extern* ; Palanca, A. ; Soto, H. ; Llarena, I. ; DeGrave, A. N. ; Guedes, G. ; Henrique de Oliveira, G. ; Coelho Conceicao, A. L.Extern*DESY* ; Mieites, V. ; Icardo, J. M. ; Sanchez-Cano, C. ; Conde, O. M. ; Lutz, S. ; Cortajarena, A. L.Extern* ; Villar, A. V. (Corresponding author)Extern*

2025
Elsevier St. Louis

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Please use a persistent id in citations: doi:10.1016/j.isci.2025.113013  doi:10.3204/PUBDB-2025-04941

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 TGFβ1-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.

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Contributing Institute(s):

1. DOOR-User (DOOR ; HAS-User)
2. PETRA-D (FS-PETRA-D)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
3. FS-Proposal: I-20210691 EC (I-20210691-EC) (I-20210691-EC)
4. FS-Proposal: I-20220193 EC (I-20220193-EC) (I-20220193-EC)

Experiment(s):

1. PETRA Beamline P62 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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