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000641210 1001_ $$0P:(DE-H253)PIP1096413$$aMaestro, David$$b0
000641210 245__ $$aCardiac fibrosis inhibitor CTPR390 prevents structural and morphological changes in human engineered cardiac connective tissue
000641210 260__ $$aSt. Louis$$bElsevier$$c2025
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000641210 520__ $$aCardiac 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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000641210 7001_ $$aPalanca, Ana$$b1
000641210 7001_ $$aSoto, Helena$$b2
000641210 7001_ $$aLlarena, I.$$b3
000641210 7001_ $$aDeGrave, Alisa Nicole$$b4
000641210 7001_ $$aGuedes, Gabriela$$b5
000641210 7001_ $$aHenrique de Oliveira, Guilherme$$b6
000641210 7001_ $$0P:(DE-H253)PIP1016756$$aCoelho Conceicao, Andre Luiz$$b7
000641210 7001_ $$aMieites, Verónica$$b8
000641210 7001_ $$aIcardo, Jose M.$$b9
000641210 7001_ $$aSanchez-Cano, Carlos$$b10
000641210 7001_ $$aConde, Olga M.$$b11
000641210 7001_ $$aLutz, Susanne$$b12
000641210 7001_ $$0P:(DE-H253)PIP1096302$$aCortajarena, Aitziber L.$$b13
000641210 7001_ $$0P:(DE-H253)PIP1096395$$aVillar, Ana V$$b14$$eCorresponding author
000641210 773__ $$0PERI:(DE-600)2927064-9$$a10.1016/j.isci.2025.113013$$gVol. 28, no. 8, p. 113013 -$$n8$$p113013 $$tiScience$$v28$$x2589-0042$$y2025
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