Key result
CTPR390 prevented architectural changes in TGFβ1-activated engineered connective tissue, significantly reducing tissue stiffness (p<0.0001) and lowering pro-fibrotic gene and protein expression.
Why the study?
Cardiac fibrosis lacks effective treatment, and the experimental anti-fibrotic Hsp90 inhibitor CTPR390, while successful in animal models, remained unexplored in human cardiac models.
p-value: p=<0.0001
In a 3D human engineered connective tissue model, the Hsp90 inhibitor CTPR390 successfully prevented TGFβ1-induced fibrotic structural and biomechanical changes, highlighting its potential as a novel anti-fibrotic therapy for heart failure.
CTPR390 reduces fibrosis in 3D human cardiac models; leaves open translation to clinical heart failure therapy.
Cardiac fibrosis is a key characteristic of heart failure, with no effective treatment available. Using three-dimensional human models and cutting-edge biotechnology to evaluate new therapies offers a significant advancement. CTPR390, an experimental anti-fibrotic inhibitor targeting Hsp90, has shown success in animal models, but remains unexplored in human cardiac models. This study evaluated a cardiac three-dimensional engineered connective tissue (ECT) model treated with CTPR390, 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 percentage of structured areas and degree of collagen structuration. Additionally, the 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.
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Maestro et al. (2025) studied Cardiac fibrosis (in vitro model). CTPR390 vs. TGFβ1-activated ECT and Control ECT was evaluated on ECT stiffness (Young's modulus) and contraction (p=<0.0001). CTPR390 prevented architectural changes in TGFβ1-activated engineered connective tissue, significantly reducing tissue stiffness (p<0.0001) and lowering pro-fibrotic gene and protein expression.
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