Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis

Ribeiro-Rodrigues, Teresa; Laundos, Tiago L.; Carvalho, Rui; Batista-Almeida, Daniela; Pereira, Ricardo Timarán; Coelho-Santos, Vanessa; Fernandes, Rosa; Zuzarte, Mónica; Enguita, Francisco J.; Costa, Marina C.; Pinto-do-Ó, Perpétua; Pinto, M.; Gouveia, Pedro; Ferreira, Lino; Mason, Justin C.; Pereira, Paulo Cesar de Souza; Kwak, Brenda R.; Nascimento, Diana S.; Girão, Henrique

doi:10.1093/cvr/cvx118

Cited by 204 publications

(173 citation statements)

References 30 publications

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“…In each case, the mechanisms of EV secretion and uptake are highly regulated, and can be affected in response to various cellular stressors, including ischaemia . Mounting evidence has demonstrated that EVs are major conveyors of biological information, being able to deliver complex mixtures of cargo in a targeted manner, modulating the behaviour of receptor cells . In the heart, EVs secreted by adult mouse cardiomyocytes were shown to modulate gene expression in fibroblasts and activate endothelial cells .…”

Section: Introductionmentioning

confidence: 99%

“…EV secretion of heat shock protein (Hsp)60, a known activator of toll‐like receptor (TLR)4, by cardiomyocytes was reported to be upregulated in response to hypoxia . Recently, we showed that cardiomyocytes subjected to ischaemia release EVs that promote the growth of new vessels in the heart . Nevertheless, cardiomyocyte‐macrophage crosstalk via EVs remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Ischaemia alters the effects of cardiomyocyte‐derived extracellular vesicles on macrophage activation

Paiva

Martins‐Marques

Jesus

et al. 2018

J Cellular Molecular Medi

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Myocardial ischaemia is associated with an exacerbated inflammatory response, as well as with a deregulation of intercellular communication systems. Macrophages have been implicated in the maintenance of heart homeostasis and in the progression and resolution of the ischaemic injury. Nevertheless, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages remain largely underexplored. Extracellular vesicles (EVs) have emerged as key players of cell‐cell communication in cardiac health and disease. Hence, the main objective of this study was to characterize the impact of cardiomyocyte‐derived EVs upon macrophage activation. Results obtained demonstrate that EVs released by H9c2 cells induced a pro‐inflammatory profile in macrophages, via p38MAPK activation and increased expression of iNOS, IL‐1β and IL‐6, being these effects less pronounced with ischaemic EVs. EVs derived from neonatal cardiomyocytes, maintained either in control or ischaemia, induced a similar pattern of p38MAPK activation, expression of iNOS, IL‐1β, IL‐6, IL‐10 and TNFα. Importantly, adhesion of macrophages to fibronectin was enhanced by EVs released by cardiomyocytes under ischaemia, whereas phagocytic capacity and adhesion to cardiomyocytes were higher in macrophages incubated with control EVs. Additionally, serum‐circulating EVs isolated from human controls or acute myocardial infarction patients induce macrophage activation.According to our model, in basal conditions, cardiomyocyte‐derived EVs maintain a macrophage profile that ensure heart homeostasis, whereas during ischaemia, this crosstalk is affected, likely impacting healing and post‐infarction remodelling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ischaemia alters the effects of cardiomyocyte‐derived extracellular vesicles on macrophage activation

Paiva

Martins‐Marques

Jesus

et al. 2018

J Cellular Molecular Medi

Self Cite

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“…H9C2 myoblasts subject to hypoxic conditions secrete exosomes enriched for miRs related to cell proliferation and differentiation including miR‐143 and miR‐222. In corollary experiments, the exosomes derived from the hypoxic cells induced endothelial proliferation, migration, and survival under stress …”

Section: Understanding the Paracrine Effects Exerted By Exosomes Secrmentioning

confidence: 98%

“…The effects of cardiomyocyte‐derived exosomes were either proangiogenic or antiangiogenic, dependent on the conditions of release, which affected their miR cargo. Cardiomyocyte‐secreted exosomes were also found to be involved in the transfer of functional angiotensin II type 1 receptors ( AT 1Rs) under conditions of stress and involved in HSP 90 (heat shock 90‐kDa protein)–dependent regulation of collagen synthesis in fibroblasts in models of hypertrophy . Serum and plasma exosomes arise from a variety of cell sources, and the diversity of their effects results from the disease status and conditions of release.…”

Section: Understanding the Paracrine Effects Exerted By Exosomes Secrmentioning

confidence: 99%

Examining the Paracrine Effects of Exosomes in Cardiovascular Disease and Repair

Gartz

Strande

2018

JAHA

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“…Although gastric cancer biomarkers and theranostics have made great advance [23,24,25,26]; some miRNAs have also been found to be associated with gastric cancer stages [27], how the exosomal proteins involved in the progression of cancer still lacks report. Li, et al reported that exosomal proteins were used for cancer diagnosis, were potential biomarkers [28], and could also be used for cardiac angiogenesis [29], tumor therapy [30] and (hepatitis B virus) HBV therapy [31]. Tumor cell-derived exosomes could be used for tumor therapy [32].…”

Section: Urinary Exosomes Proteomics Analysismentioning

confidence: 99%

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Yang¹,

Zhi²,

Liu³

et al. 2017

Nano BioMed ENG

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Urinary exosomes containing specific biomarkers have recently been considered as novel potential non-invasive candidates for renal disease diagnosis. However, the development of urinary exosomes in basic research and their subsequent diagnostic application are impeded by the lack of an efficient isolation method. One of the main challenges during urinary exosomes isolation is how to remove a large number of Tamm Horsfall proteins (around 92 kDa) and other biological components from exosome enrichment mixture. Herein, we report a facile and low-cost isolation method for highlypurified human urinary exosomes based on dialysis. The key protocol for exosome isolation includes only two steps: (1) Healthy person urines were collected. 10 mL urine in 300 kDa dialysis tubes was firstly dialyzed in phosphate-buffered saline solution three times for sequential nine hours; (2) The dialysis suspension was concentrated to 200 μL by using 100 kDa ultracentrifuge tubes to achieve urinary exosome isolation. For verification, the concentrated solution was examined by western blot, transmission electronic microscopy, atomic force microscopy and qNano, which demonstrated the highly-purified urinary exosomes were present. Furthermore, a total of 359 proteins were identified by the proteomic analysis of purified urinary exosomes from healthy persons. Those results demonstrated that highly-purified urinary exosomes could be achieved by our isolation method; 359 proteins were identified from healthy persons. Further works will focus on screening and identifying disease-related biomarkers from human urine exosomes for clinical diagnosis.

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Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis

Abstract: 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.

Cited by 204 publications

References 30 publications

Ischaemia alters the effects of cardiomyocyte‐derived extracellular vesicles on macrophage activation

Ischaemia alters the effects of cardiomyocyte‐derived extracellular vesicles on macrophage activation

Examining the Paracrine Effects of Exosomes in Cardiovascular Disease and Repair

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

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