Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes

Takeshi Fujisawa; Keqing Wang; Xi-Lin Niu; Stuart Egginton; Shakil Ahmad; Peter W. Hewett; Christopher D. Kontos; Asif Ahmed

doi:10.1093/cvr/cvw223

Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1⁺ monocytes

Takeshi Fujisawa, Keqing Wang, Xi-Lin Niu, Stuart Egginton, Shakil Ahmad, Peter W. Hewett, Christopher D. Kontos, Asif Ahmed^*

^*Corresponding author for this work

Aston Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

Aims

Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.

Methods and results

Apo-E knockout (Apo-E^-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1⁺monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.

Conclusions

Ang-1 specifically increases circulating Gr1⁺inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.

Original language	English
Pages (from-to)	81-89
Number of pages	9
Journal	Cardiovascular Research
Volume	113
Issue number	1
DOIs	https://doi.org/10.1093/cvr/cvw223
Publication status	Published - 17 Oct 2017

Bibliographical note

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Funding: British Heart Foundation (PG/06/114); MRC (G0601295 and G0700288); NIH (R01 HL70165); and Mid-Atlantic Affiliate of the American Heart Association (0355792U)

Keywords

angiopoietin-1
atherosclerosis
monocytes

Access to Document

10.1093/cvr/cvw223Licence: CC BY 3.0

Angiopoietin-1 promotes atherosclerosis
© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 513 KBLicence: CC BY 3.0

Cite this

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title = "Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes",

abstract = "AimsAtherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.Methods and resultsApo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.ConclusionsAng-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.",

keywords = "angiopoietin-1, atherosclerosis, monocytes",

author = "Takeshi Fujisawa and Keqing Wang and Xi-Lin Niu and Stuart Egginton and Shakil Ahmad and Hewett, {Peter W.} and Kontos, {Christopher D.} and Asif Ahmed",

note = "{\textcopyright} The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: British Heart Foundation (PG/06/114); MRC (G0601295 and G0700288); NIH (R01 HL70165); and Mid-Atlantic Affiliate of the American Heart Association (0355792U)",

year = "2017",

month = oct,

day = "17",

doi = "10.1093/cvr/cvw223",

language = "English",

volume = "113",

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T1 - Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes

AU - Fujisawa, Takeshi

AU - Wang, Keqing

AU - Niu, Xi-Lin

AU - Egginton, Stuart

AU - Ahmad, Shakil

AU - Hewett, Peter W.

AU - Kontos, Christopher D.

AU - Ahmed, Asif

N1 - © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: British Heart Foundation (PG/06/114); MRC (G0601295 and G0700288); NIH (R01 HL70165); and Mid-Atlantic Affiliate of the American Heart Association (0355792U)

PY - 2017/10/17

Y1 - 2017/10/17

N2 - AimsAtherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.Methods and resultsApo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.ConclusionsAng-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.

AB - AimsAtherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.Methods and resultsApo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.ConclusionsAng-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.

KW - angiopoietin-1

KW - atherosclerosis

KW - monocytes

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