Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation.

Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation / Garoffolo, Gloria; Casaburo, Manuel; Amadeo, Francesco; Salvi, Massimo; Bernava, Giacomo; Piacentini, Luca; Chimenti, Isotta; Zaccagnini, Germana; Milcovich, Gesmi; Zuccolo, Estella; Agrifoglio, Marco; Ragazzini, Sara; Baasansuren, Otgon; Cozzolino, Claudia; Chiesa, Mattia; Ferrari, Silvia; Carbonaro, Dario; Santoro, Rosaria; Manzoni, Martina; Casalis, Loredana; Raucci, Angela; Molinari, Filippo; Menicanti, Lorenzo; Pagano, Francesca; Ohashi, Toshiro; Martelli, Fabio; Massai, Diana; Colombo, Gualtiero I; Messina, Elisa; Morbiducci, Umberto; Pesce, Maurizio. - In: CIRCULATION RESEARCH. - ISSN 0009-7330. - STAMPA. - 131:3(2022), pp. 239-257. [10.1161/CIRCRESAHA.121.319373]

Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation

Salvi, Massimo;Carbonaro, Dario;Molinari, Filippo;Massai, Diana;Morbiducci, Umberto;
2022

Abstract

Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation.
File in questo prodotto:
File Dimensione Formato  
Garoffolo et al R2.pdf

Open Access dal 03/01/2023

Tipologia: 2. Post-print / Author's Accepted Manuscript
Licenza: Pubblico - Tutti i diritti riservati
Dimensione 4.12 MB
Formato Adobe PDF
4.12 MB Adobe PDF Visualizza/Apri
Salvi-Reduction (1).pdf

accesso riservato

Tipologia: 2a Post-print versione editoriale / Version of Record
Licenza: Non Pubblico - Accesso privato/ristretto
Dimensione 1.14 MB
Formato Adobe PDF
1.14 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11583/2970199