Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis.
- Ribeiro-Rodrigues TM Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Laundos TL Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
- Pereira-Carvalho R Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Batista-Almeida D Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Pereira R Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Coelho-Santos V Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Silva AP Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Fernandes R Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Zuzarte M Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Enguita FJ Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, 1649-028 Lisboa, Portugal.
- Costa MC Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, 1649-028 Lisboa, Portugal.
- Pinto-do-Ó P Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
- Pinto MT Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
- Gouveia P CNC.IBILI, University of Coimbra, Portugal.
- Ferreira L CNC.IBILI, University of Coimbra, Portugal.
- Mason JC Vascular Sciences Unit, Imperial Centre for Translational & Experimental Medicine, Imperial College London, London, UK.
- Pereira P Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- Kwak BR Department of Pathology and Immunology, and Department of Medical Specialties-Cardiology, University of Geneva, CH-1211 Geneva, Switzerland.
- Nascimento DS Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
- Girão H Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
- 2017-09-02
Published in:
- Cardiovascular research. - 2017
Angiogenesis
Coronary collateral circulation
Exosomes
Extracellular vesicles
Ischaemia
Myocardial infarction
Animals
Biological Transport
Cell Movement
Cells, Cultured
Endothelial Cells
Exosomes
Morphogenesis
Myocardial Infarction
Myocardium
Myocytes, Cardiac
Neovascularization, Pathologic
Rats, Wistar
English
Aims
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1093/cvr/cvx118
- PMID 28859292
- Persistent URL
- https://sonar.ch/global/documents/232651
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