Cardiac fibrosis inhibitor CTPR390 prevents structural and morphological changes in collagen and fibroblasts of engineered human connective tissue

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 connective tissue (ECT) model, focusing on changes in the extracellular matrix and fibroblasts. Results showed that CTPR390 prevented architectural changes in TGFβ1-activated ECT, preserving tissue perimeter, collagen fibers alignment while reducing structured areas and degree of collagen structuration. CTPR390 treatment reduced cell area of elongated 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 ECT. This treatment also lowered the gene and protein expression of key pro-fibrotic markers. For the first time, 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.