Cardiac adverse remodeling is characterized by biological changes that aect the composition and architecture of the extracellular matrix (ECM). The consequently disrupted signaling can interfere with the balance between cardiogenic and pro-fibrotic phenotype of resident cardiac stromal primitive cells (CPCs). The latter are important players in cardiac homeostasis and can be exploited as therapeutic cells in regenerative medicine. Our aim was to compare the eects of human decellularized native ECM from normal (dECM-NH) or failing hearts (dECM-PH) on human CPCs. CPCs were cultured on dECM sections and characterized for gene expression, immunofluorescence, and paracrine profiles. When cultured on dECM-NH, CPCs significantly upregulated cardiac commitment markers (CX43, NKX2.5), cardioprotective cytokines (bFGF, HGF), and the angiogenesis mediator, NO. When seeded on dECM-PH, instead, CPCs upregulated pro-remodeling cytokines (IGF-2, PDGF-AA, TGF-) and the oxidative stress molecule H2O2. Interestingly, culture on dECM-PH was associated with impaired paracrine support to angiogenesis, and increased expression of the vascular endothelial growth factor (VEGF)-sequestering decoy isoform of the KDR/VEGFR2 receptor. Our results suggest that resident CPCs exposed to the pathological microenvironment of remodeling ECM partially lose their paracrine angiogenic properties and release more pro-fibrotic cytokines. These observations shed novel insights on the crosstalk between ECM and stromal CPCs, suggesting also a cautious use of non-healthy decellularized myocardium for cardiac tissue engineering approaches.

The microenvironment of decellularized extracellular matrix from heart failure myocardium alters the balance between angiogenic and fibrotic signals from stromal primitive cells / Belviso, Immacolata; Angelini, Francesco; Di Meglio, Franca; Picchio, Vittorio; Sacco, Anna Maria; Nocella, Cristina; Romano, Veronica; Nurzynska, Daria; Frati, Giacomo; Maiello, Ciro; Messina, Elisa; Montagnani, Stefania; Pagano, Francesca; Castaldo, Clotilde; Chimenti, Isotta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:21(2020), pp. 1-18. [10.3390/ijms21217903]

The microenvironment of decellularized extracellular matrix from heart failure myocardium alters the balance between angiogenic and fibrotic signals from stromal primitive cells

Angelini, Francesco;Picchio, Vittorio;Nocella, Cristina;Frati, Giacomo;Messina, Elisa;Castaldo, Clotilde;Chimenti, Isotta
Ultimo
2020

Abstract

Cardiac adverse remodeling is characterized by biological changes that aect the composition and architecture of the extracellular matrix (ECM). The consequently disrupted signaling can interfere with the balance between cardiogenic and pro-fibrotic phenotype of resident cardiac stromal primitive cells (CPCs). The latter are important players in cardiac homeostasis and can be exploited as therapeutic cells in regenerative medicine. Our aim was to compare the eects of human decellularized native ECM from normal (dECM-NH) or failing hearts (dECM-PH) on human CPCs. CPCs were cultured on dECM sections and characterized for gene expression, immunofluorescence, and paracrine profiles. When cultured on dECM-NH, CPCs significantly upregulated cardiac commitment markers (CX43, NKX2.5), cardioprotective cytokines (bFGF, HGF), and the angiogenesis mediator, NO. When seeded on dECM-PH, instead, CPCs upregulated pro-remodeling cytokines (IGF-2, PDGF-AA, TGF-) and the oxidative stress molecule H2O2. Interestingly, culture on dECM-PH was associated with impaired paracrine support to angiogenesis, and increased expression of the vascular endothelial growth factor (VEGF)-sequestering decoy isoform of the KDR/VEGFR2 receptor. Our results suggest that resident CPCs exposed to the pathological microenvironment of remodeling ECM partially lose their paracrine angiogenic properties and release more pro-fibrotic cytokines. These observations shed novel insights on the crosstalk between ECM and stromal CPCs, suggesting also a cautious use of non-healthy decellularized myocardium for cardiac tissue engineering approaches.
2020
Extracellular matrix; cardiac stromal cells; microenvironment; cardiac fibrosis; paracrine signals; KDR/VEGFR2
01 Pubblicazione su rivista::01a Articolo in rivista
The microenvironment of decellularized extracellular matrix from heart failure myocardium alters the balance between angiogenic and fibrotic signals from stromal primitive cells / Belviso, Immacolata; Angelini, Francesco; Di Meglio, Franca; Picchio, Vittorio; Sacco, Anna Maria; Nocella, Cristina; Romano, Veronica; Nurzynska, Daria; Frati, Giacomo; Maiello, Ciro; Messina, Elisa; Montagnani, Stefania; Pagano, Francesca; Castaldo, Clotilde; Chimenti, Isotta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:21(2020), pp. 1-18. [10.3390/ijms21217903]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1461918
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