Browsing by Author "Laundos, Tiago L."
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- Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesisPublication . Ribeiro-Rodrigues, Teresa M.; Laundos, Tiago L.; Pereira-Carvalho, Rita; Batista-Almeida, Daniela; Pereira, Ricardo; Coelho-Santos, Vanessa; Silva, Ana P.; Fernandes, Rosa; Zuzarte, Monica; Enguita, Francisco J.; Costa, Marina C.; Pinto-do-Ó, Perpetua; Pinto, Marta T.; Gouveia, Pedro; Ferreira, Lino; Mason, Justin C.; Pereira, Paulo; Kwak, Brenda R.; Nascimento, Diana S.; Girão, HenriqueAims: Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide and results from an obstruction in the blood supply to a region of the heart. In an attempt to replenish oxygen and nutrients to the deprived area, affected cells release signals to promote the development of new vessels and confer protection against MI. However, the mechanisms underlying the growth of new vessels in an ischaemic scenario remain poorly understood. Here, we show that cardiomyocytes subjected to ischaemia release exosomes that elicit an angiogenic response of endothelial cells (ECs). Methods and results: Exosomes secreted by H9c2 myocardial cells and primary cardiomyocytes, cultured either in control or ischaemic conditions were isolated and added to ECs. We show that ischaemic exosomes, in comparison with control exosomes, confer protection against oxidative-induced lesion, promote proliferation, and sprouting of ECs, stimulate the formation of capillary-like structures and strengthen adhesion complexes and barrier properties. Moreover, ischaemic exosomes display higher levels of metalloproteases (MMP) and promote the secretion of MMP by ECs. We demonstrate that miR-222 and miR-143, the relatively most abundant miRs in ischaemic exosomes, partially recapitulate the angiogenic effect of exosomes. Additionally, we show that ischaemic exosomes stimulate the formation of new functional vessels in vivo using in ovo and Matrigel plug assays. Finally, we demonstrate that intramyocardial delivery of ischaemic exosomes improves neovascularization following MI. Conclusions: This study establishes that exosomes secreted by cardiomyocytes under ischaemic conditions promote heart angiogenesis, which may pave the way towards the development of add-on therapies to enhance myocardial blood supply.
- Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local FibrosisPublication . Sampaio-Pinto, Vasco; Rodrigues, Sílvia C.; Laundos, Tiago L.; Silva, Elsa D.; Vasques-Nóvoa, Francisco; Silva, Ana C.; Cerqueira, Rui J.; Resende, Tatiana P.; Pianca, Nicola; Leite-Moreira, Adelino; D'Uva, Gabriele; Thorsteinsdottir, Solveig; Pinto-do-Ó, Perpétua; Nascimento, Diana S.So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis.