Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2
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...
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| Format: | Online |
| Language: | English |
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BlackWell Publishing Ltd
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409030/ |
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pubmed-4409030 |
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pubmed-44090302015-04-29 Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 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 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 β2, 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 β2 function on HSPC. In addition, integrin β2 function could be regulated via ERK-independent LRP1 pathway. Integrin β2 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| 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 |
| spellingShingle |
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 β2 |
| 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 |
| title |
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 |
| title_short |
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 |
| title_full |
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 |
| title_fullStr |
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 |
| title_full_unstemmed |
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2 |
| title_sort |
hematopoietic stem/progenitor cells directly contribute to arteriosclerotic progression via integrin β2 |
| 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 β2, 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 β2 function on HSPC. In addition, integrin β2 function could be regulated via ERK-independent LRP1 pathway. Integrin β2 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 |
| publisher |
BlackWell Publishing Ltd |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409030/ |
| _version_ |
1613215415157129216 |