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Open AccessArticle

The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells

1
Department of Public Health, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
2
Experimental and Clinical Pharmacology Unit, CRO-National Cancer Institute, 33081 Aviano (PN), Italy
3
Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Corso della Repubblica 79, 04100 Latina, Italy
4
Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy
5
Department of AngioCardioNeurology, IRCCS Neuromed, 86077 Pozzilli, Italy
6
Department of Cardiovascular Surgery and Transplant, Monaldi Hospital, 80131 Naples, Italy
7
Department of Maternal Infantile and Urological Sciences, “Umberto I” Hospital, 00161 Rome, Italy
8
Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), 00015 Monterotondo (RM), Italy
9
Mediterranea Cardiocentro, 80122 Napoli, Italy
*
Author to whom correspondence should be addressed.
Equal contribution.
Equal contribution.
Int. J. Mol. Sci. 2020, 21(21), 7903; https://doi.org/10.3390/ijms21217903
Received: 2 October 2020 / Revised: 21 October 2020 / Accepted: 22 October 2020 / Published: 24 October 2020
Cardiac adverse remodeling is characterized by biological changes that affect 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 effects 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-β) 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. View Full-Text
Keywords: extracellular matrix; cardiac stromal cells; microenvironment; cardiac fibrosis; paracrine signals; KDR/VEGFR2 extracellular matrix; cardiac stromal cells; microenvironment; cardiac fibrosis; paracrine signals; KDR/VEGFR2
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MDPI and ACS Style

Belviso, I.; Angelini, F.; Di Meglio, F.; Picchio, V.; Sacco, A.M.; Nocella, C.; Romano, V.; Nurzynska, D.; Frati, G.; Maiello, C.; Messina, E.; Montagnani, S.; Pagano, F.; Castaldo, C.; Chimenti, I. The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells. Int. J. Mol. Sci. 2020, 21, 7903. https://doi.org/10.3390/ijms21217903

AMA Style

Belviso I, Angelini F, Di Meglio F, Picchio V, Sacco AM, Nocella C, Romano V, Nurzynska D, Frati G, Maiello C, Messina E, Montagnani S, Pagano F, Castaldo C, Chimenti I. The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells. International Journal of Molecular Sciences. 2020; 21(21):7903. https://doi.org/10.3390/ijms21217903

Chicago/Turabian Style

Belviso, Immacolata; Angelini, Francesco; Di Meglio, Franca; Picchio, Vittorio; Sacco, Anna M.; Nocella, Cristina; Romano, Veronica; Nurzynska, Daria; Frati, Giacomo; Maiello, Ciro; Messina, Elisa; Montagnani, Stefania; Pagano, Francesca; Castaldo, Clotilde; Chimenti, Isotta. 2020. "The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells" Int. J. Mol. Sci. 21, no. 21: 7903. https://doi.org/10.3390/ijms21217903

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