Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice in Vivo

Cheng Xue Qin, Siobhan B. Finlayson, Annas Ai-Sharea, Mitchel Tate, Miles J. De Blasio, Minh Deo, Sarah Rosli, Darnel Prakoso, Colleen J. Thomas, Helen Kiriazis, Eleanor Gould, Yuan H. Yang, Eric F. Morand, Mauro Perretti, Andrew J. Murphy, Xiao Jun Du, Xiao Ming Gao, Rebecca H. Ritchie

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number16615
Number of pages14
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Cite this

Qin, Cheng Xue ; Finlayson, Siobhan B. ; Ai-Sharea, Annas ; Tate, Mitchel ; De Blasio, Miles J. ; Deo, Minh ; Rosli, Sarah ; Prakoso, Darnel ; Thomas, Colleen J. ; Kiriazis, Helen ; Gould, Eleanor ; Yang, Yuan H. ; Morand, Eric F. ; Perretti, Mauro ; Murphy, Andrew J. ; Du, Xiao Jun ; Gao, Xiao Ming ; Ritchie, Rebecca H. / Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice in Vivo. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{fe36257408d145049f461610aa2a9373,
title = "Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice in Vivo",
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.",
author = "Qin, {Cheng Xue} and Finlayson, {Siobhan B.} and Annas Ai-Sharea and Mitchel Tate and {De Blasio}, {Miles J.} and Minh Deo and Sarah Rosli and Darnel Prakoso and Thomas, {Colleen J.} and Helen Kiriazis and Eleanor Gould and Yang, {Yuan H.} and Morand, {Eric F.} and Mauro Perretti and Murphy, {Andrew J.} and Du, {Xiao Jun} and Gao, {Xiao Ming} and Ritchie, {Rebecca H.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-16317-1",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice in Vivo. / Qin, Cheng Xue; Finlayson, Siobhan B.; Ai-Sharea, Annas; Tate, Mitchel; De Blasio, Miles J.; Deo, Minh; Rosli, Sarah; Prakoso, Darnel; Thomas, Colleen J.; Kiriazis, Helen; Gould, Eleanor; Yang, Yuan H.; Morand, Eric F.; Perretti, Mauro; Murphy, Andrew J.; Du, Xiao Jun; Gao, Xiao Ming; Ritchie, Rebecca H.

In: Scientific Reports, Vol. 7, No. 1, 16615, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and Inflammatory Response Post Myocardial Infarction in Mice in Vivo

AU - Qin, Cheng Xue

AU - Finlayson, Siobhan B.

AU - Ai-Sharea, Annas

AU - Tate, Mitchel

AU - De Blasio, Miles J.

AU - Deo, Minh

AU - Rosli, Sarah

AU - Prakoso, Darnel

AU - Thomas, Colleen J.

AU - Kiriazis, Helen

AU - Gould, Eleanor

AU - Yang, Yuan H.

AU - Morand, Eric F.

AU - Perretti, Mauro

AU - Murphy, Andrew J.

AU - Du, Xiao Jun

AU - Gao, Xiao Ming

AU - Ritchie, Rebecca H.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85036626427&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-16317-1

DO - 10.1038/s41598-017-16317-1

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 16615

ER -