14 Telomerase and myocardin co-expressing mesenchymal cells increase survival and induce cardiac and vascular markers in cardiac stromal cells undergoing simulated ischemia/reperfusion. (8th December 2021)

• Record Type: Journal Article
• Authors: Madonna, Rosalinda; Guarnieri, Simone; Kovacshazi, Csenger; Gorbe, Aniko; Giricz, Zoltan; Geng, Yong-Jian; Mariggiò, Maria Addolorata; Ferdinandy, Peter; De Caterina, Raffaele
• Is Part Of: European heart journal supplements. Volume 23(2021)Supplement G
• Publication Date: 2021-12-08
• Subjects: Cardiology -- Periodicals; Cardiology -- Europe -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/suab138.004
• Languages: English
• ISSNs: 1520-765X

Abstract

Abstract: Aims: Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favouring their paracrine activities. To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs). Methods: Murine CSCs were isolated with the cardiosphere (CSps) isolation technique. Results: T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28 ± 4 vs. 10 ± 3%, P = 0.02). Pre-treatment with CM (15 ± 2, P = 0.02) or with the EV-enriched fraction (10 ± 1%, P = 0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more pronounced with CM (7 ± 1%, P = 0.01) or the EV-enriched fraction (2 ± 1%, P = 0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin. Conclusions: The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.