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Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2)
Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to infl...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409030/ https://www.ncbi.nlm.nih.gov/pubmed/25546260 http://dx.doi.org/10.1002/stem.1939 |
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author | Wang, Xuhong Gao, Mingming Schouteden, Sarah Roebroek, Anton Eggermont, Kristel van Veldhoven, Paul P Liu, George Peters, Thorsten Scharffetter-Kochanek, Karin Verfaillie, Catherine M Feng, Yingmei |
author_facet | Wang, Xuhong Gao, Mingming Schouteden, Sarah Roebroek, Anton Eggermont, Kristel van Veldhoven, Paul P Liu, George Peters, Thorsten Scharffetter-Kochanek, Karin Verfaillie, Catherine M Feng, Yingmei |
author_sort | Wang, Xuhong |
collection | PubMed |
description | Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to inflammation and neointima formation. We demonstrated that Lin(−) Sca-1(+) cKit(+) (LSK cells) in BM and peripheral blood of LDLr(−/−) mice on high fat diet expressed significantly more integrin β(2), which was responsible for LSK cell adhesion and migration toward ICAM-1 in vitro, and homing to injured arteries in vivo, all of which were blocked with an anti-CD18 blocking antibody. When homed LSK cells were isolated from ligated artery and injected to irradiated recipients, they resulted in BM reconstitution. Injection of CD18(+/+) LSK cells to immunodeficient Balb/C Rag2(−) γC(−/−) recipients resulted in more severe inflammation and reinforced neointima formation in the ligated carotid artery, compared to mice injected with PBS and CD18(−/−) LSK cells. Hypercholesterolemia stimulated ERK phosphorylation (pERK) in LSK cells of LDLr(−/−) mice in vivo. Blockade of pERK reduced ARF1 expression, leading to decreased integrin β(2) function on HSPC. In addition, integrin β(2) function could be regulated via ERK-independent LRP1 pathway. Integrin β(2) expression on HSPC is regulated by hypercholesterolemia, specifically LDL, in pERK-dependent and -independent manners, leading to increased homing and localization of HSPC to injured arteries, which is highly correlated with arteriosclerosis. Stem Cells 2015;33:1230–1240 |
format | Online Article Text |
id | pubmed-4409030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44090302015-04-29 Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) Wang, Xuhong Gao, Mingming Schouteden, Sarah Roebroek, Anton Eggermont, Kristel van Veldhoven, Paul P Liu, George Peters, Thorsten Scharffetter-Kochanek, Karin Verfaillie, Catherine M Feng, Yingmei Stem Cells Translational and Clinical Research Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to inflammation and neointima formation. We demonstrated that Lin(−) Sca-1(+) cKit(+) (LSK cells) in BM and peripheral blood of LDLr(−/−) mice on high fat diet expressed significantly more integrin β(2), which was responsible for LSK cell adhesion and migration toward ICAM-1 in vitro, and homing to injured arteries in vivo, all of which were blocked with an anti-CD18 blocking antibody. When homed LSK cells were isolated from ligated artery and injected to irradiated recipients, they resulted in BM reconstitution. Injection of CD18(+/+) LSK cells to immunodeficient Balb/C Rag2(−) γC(−/−) recipients resulted in more severe inflammation and reinforced neointima formation in the ligated carotid artery, compared to mice injected with PBS and CD18(−/−) LSK cells. Hypercholesterolemia stimulated ERK phosphorylation (pERK) in LSK cells of LDLr(−/−) mice in vivo. Blockade of pERK reduced ARF1 expression, leading to decreased integrin β(2) function on HSPC. In addition, integrin β(2) function could be regulated via ERK-independent LRP1 pathway. Integrin β(2) expression on HSPC is regulated by hypercholesterolemia, specifically LDL, in pERK-dependent and -independent manners, leading to increased homing and localization of HSPC to injured arteries, which is highly correlated with arteriosclerosis. Stem Cells 2015;33:1230–1240 BlackWell Publishing Ltd 2015-04 2015-03-24 /pmc/articles/PMC4409030/ /pubmed/25546260 http://dx.doi.org/10.1002/stem.1939 Text en © 2014 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf AlphaMed Press http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Translational and Clinical Research Wang, Xuhong Gao, Mingming Schouteden, Sarah Roebroek, Anton Eggermont, Kristel van Veldhoven, Paul P Liu, George Peters, Thorsten Scharffetter-Kochanek, Karin Verfaillie, Catherine M Feng, Yingmei Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title | Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title_full | Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title_fullStr | Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title_full_unstemmed | Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title_short | Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β(2) |
title_sort | hematopoietic stem/progenitor cells directly contribute to arteriosclerotic progression via integrin β(2) |
topic | Translational and Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409030/ https://www.ncbi.nlm.nih.gov/pubmed/25546260 http://dx.doi.org/10.1002/stem.1939 |
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