dc.contributor.author | Qin, CX | en_US |
dc.contributor.author | Finlayson, SB | en_US |
dc.contributor.author | Al-Sharea, A | en_US |
dc.contributor.author | Tate, M | en_US |
dc.contributor.author | De Blasio, MJ | en_US |
dc.contributor.author | Deo, M | en_US |
dc.contributor.author | Rosli, S | en_US |
dc.contributor.author | Prakoso, D | en_US |
dc.contributor.author | Thomas, CJ | en_US |
dc.contributor.author | Kiriazis, H | en_US |
dc.contributor.author | Gould, E | en_US |
dc.contributor.author | Yang, YH | en_US |
dc.contributor.author | Morand, EF | en_US |
dc.contributor.author | Perretti, M | en_US |
dc.contributor.author | Murphy, AJ | en_US |
dc.contributor.author | Du, X-J | en_US |
dc.contributor.author | Gao, X-M | en_US |
dc.contributor.author | Ritchie, RH | en_US |
dc.date.accessioned | 2018-03-07T13:17:44Z | |
dc.date.available | 2017-11-09 | en_US |
dc.date.issued | 2017-11-30 | en_US |
dc.date.submitted | 2018-02-19T13:20:49.492Z | |
dc.identifier.other | 10.1038/s41598-017-16317-1 | |
dc.identifier.uri | https://www.nature.com/articles/s41598-017-16317-1.pdf | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/34424 | |
dc.description.abstract | Endogenous anti-inflammatory annexin-A1 (ANX-A1) plays an important role in preserving left ventricular (LV) viability and function after ischaemic insults in vitro, but its long-term cardioprotective actions in vivo are largely unknown. We tested the hypothesis that ANX-A1-deficiency exaggerates inflammation, haematopoietic stem progenitor cell (HSPC) activity and LV remodelling in response to myocardial ischaemia in vivo. Adult ANX - A1 -/- mice subjected to coronary artery occlusion exhibited increased infarct size and LV macrophage content after 24-48 h reperfusion compared with wildtype (WT) counterparts. In addition, ANX - A1 -/- mice exhibited greater expansion of HSPCs and altered pattern of HSPC mobilisation 8 days post-myocardial infarction, with increased circulating neutrophils and platelets, consistent with increased cardiac inflammation as a result of increased myeloid invading injured myocardium in response to MI. Furthermore, ANX - A1 -/- mice exhibited significantly increased expression of LV pro-inflammatory and pro-fibrotic genes and collagen deposition after MI compared to WT counterparts. ANX-A1-deficiency increased cardiac necrosis, inflammation, hypertrophy and fibrosis following MI, accompanied by exaggerated HSPC activity and impaired macrophage phenotype. These findings suggest that endogenous ANX-A1 regulates mobilisation and differentiation of HSPCs. Limiting excessive monocyte/neutrophil production may limit LV damage in vivo. Our findings support further development of novel ANX-A1-based therapies to improve cardiac outcomes after MI. | en_US |
dc.description.sponsorship | This work was supported in part by both the National Health and Medical Research Council (NHMRC) of Australia, including APP1045140 (to R.H.R., X.M.G., Y.H.Y.), APP1083138 & APP1106154 (to A.J.M.), and the Victorian Government’s Operational Infrastructure Support Program. R.H.R. and X.J.D. are NHMRC Senior Research Fellows (APP1059960; APP1043026 respectively), A.J.M. is an NHMRC Career Development Fellow (APP1085752) and a NHF Future Leader Fellow (100440). A.A.S. and S.B.F. are supported by Australian Postgraduate Awards. | en_US |
dc.format.extent | 16615 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Sci Rep | en_US |
dc.rights | Creative Commons Attribution License | |
dc.subject | Animals | en_US |
dc.subject | Annexin A1 | en_US |
dc.subject | Disease Models, Animal | en_US |
dc.subject | Hematopoietic Stem Cell Mobilization | en_US |
dc.subject | Hematopoietic Stem Cells | en_US |
dc.subject | Macrophages | en_US |
dc.subject | Male | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Knockout | en_US |
dc.subject | Myocardial Infarction | en_US |
dc.subject | Myocardial Ischemia | en_US |
dc.subject | Myocarditis | en_US |
dc.subject | Necrosis | en_US |
dc.subject | Rats | en_US |
dc.title | Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice In Vivo. | en_US |
dc.type | Article | |
dc.rights.holder | 2017 The Authors. | |
dc.identifier.doi | 10.1038/s41598-017-16317-1 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29192208 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 7 | en_US |
dcterms.dateAccepted | 2017-11-09 | en_US |