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Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis

2017Journal article Open access
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dc.contributor.authorRibeiro-Rodrigues, Teresa M.
dc.contributor.authorLaundos, Tiago L.
dc.contributor.authorPereira-Carvalho, Rita
dc.contributor.authorBatista-Almeida, Daniela
dc.contributor.authorPereira, Ricardo
dc.contributor.authorCoelho-Santos, Vanessa
dc.contributor.authorSilva, Ana P.
dc.contributor.authorFernandes, Rosa
dc.contributor.authorZuzarte, Monica
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorCosta, Marina C.
dc.contributor.authorPinto-do-Ó, Perpetua
dc.contributor.authorPinto, Marta T.
dc.contributor.authorGouveia, Pedro
dc.contributor.authorFerreira, Lino
dc.contributor.authorMason, Justin C.
dc.contributor.authorPereira, Paulo
dc.contributor.authorKwak, Brenda R.
dc.contributor.authorNascimento, Diana S.
dc.contributor.authorGirão, Henrique
dc.date.accessioned2022-09-08T13:50:25Z
dc.date.available2022-09-08T13:50:25Z
dc.date.issued2017
dc.descriptionCopyright © 2017, Oxford University Presspt_PT
dc.description.abstractAims: 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.pt_PT
dc.description.sponsorshipThis work was supported by European Regional Development Fund (FEDER) through the Operational Program for Competitiveness Factors (COMPETE) [HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323, POCI-01-0145-FEDER-016385, POCI-01-0145-FEDER-007440 to CNC.IBILI, POCI-01-0145-FEDER-007274 to i3S/INEB and NORTE-01-0145- FEDER-000012 to T.L.L.]; national funds through the Portuguese Foundation for Science and Technology (FCT) [PTDC/SAU-ORG/119296/2010, PTDC/NEU-OSD/0312/2012, PESTC/ SAU/UI3282/2013-2014, MITP-TB/ECE/0013/2013, FCT-UID/NEU/04539/2013], PD/BD/52294/2013 to T.M.R.R., SFRH/BD/85556/2012 (co-financed by QREN) to V.C.S]; Lisboa Portugal Regional Operational Programme (LISBOA 2020) and Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement; and by INFARMED Autoridade Nacional do Medicamento e Produtos de Saúde, I.P. [FIS-FIS-2015-01_CCV_20150630-157].pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCardiovasc Res. 2017 Sep 1;113(11):1338-1350pt_PT
dc.identifier.doi10.1093/cvr/cvx118pt_PT
dc.identifier.eissn1755-3245
dc.identifier.issn0008-6363
dc.identifier.urihttp://hdl.handle.net/10451/54383
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relationCENTRO-01-0145-FEDER-000012-N2323pt_PT
dc.relationPOCI-01-0145-FEDER-016385pt_PT
dc.relationPOCI-01-0145-FEDER-007440pt_PT
dc.relationPOCI-01-0145-FEDER-007274pt_PT
dc.relationNORTE-01-0145-FEDER-000012pt_PT
dc.relationUnravelling the molecular events of gap junction remodelling in ischemic heart
dc.relationPESTC/SAU/UI3282/2013-2014pt_PT
dc.relationCARDIOSTEM- Engineered cardiac tissues and stem cell-based therapies for cardiovascular applications
dc.relationCNC. IBILI
dc.relationINTER-UNIVERSITY DOCTORAL PROGRAMME IN AGEING AND CHRONIC DISEASE - Cx43 builds the bridge between endocytosis and autoph dictates the degration patway
dc.relationEFFECT OF METHYLPHENIDATE ON BLOOD-BRAIN BARRIER FUNCTION IN HEALTH AND ATTENTION DEFICIT HYPERACTIVITY DISORDER
dc.relation.publisherversionhttps://academic.oup.com/cardiovascrespt_PT
dc.subjectAngiogenesispt_PT
dc.subjectCoronary collateral circulationpt_PT
dc.subjectExosomespt_PT
dc.subjectExtracellular vesiclespt_PT
dc.subjectIschaemiapt_PT
dc.subjectMyocardial infarctionpt_PT
dc.titleExosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleUnravelling the molecular events of gap junction remodelling in ischemic heart
oaire.awardTitleCARDIOSTEM- Engineered cardiac tissues and stem cell-based therapies for cardiovascular applications
oaire.awardTitleCNC. IBILI
oaire.awardTitleINTER-UNIVERSITY DOCTORAL PROGRAMME IN AGEING AND CHRONIC DISEASE - Cx43 builds the bridge between endocytosis and autoph dictates the degration patway
oaire.awardTitleEFFECT OF METHYLPHENIDATE ON BLOOD-BRAIN BARRIER FUNCTION IN HEALTH AND ATTENTION DEFICIT HYPERACTIVITY DISORDER
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-ORG%2F119296%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FNEU-OSD%2F0312%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5665-PICT/MITP-TB%2FECE%2F0013%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FNEU%2F04539%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/PD%2FBD%2F52294%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F85556%2F2012/PT
oaire.citation.endPage1350pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1338pt_PT
oaire.citation.titleCardiovascular Researchpt_PT
oaire.citation.volume113pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream5876-PPCDTI
oaire.fundingStream5665-PICT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameEnguita
person.familyNameCosta
person.givenNameFrancisco J.
person.givenNameMarina
person.identifier173306
person.identifier.ciencia-idB215-8D49-3218
person.identifier.ciencia-id6818-7810-6CEC
person.identifier.orcid0000-0002-8072-8557
person.identifier.orcid0000-0001-9020-7539
person.identifier.ridA-2347-2009
person.identifier.ridO-1710-2014
person.identifier.scopus-author-id6602119231
person.identifier.scopus-author-id55453276400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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