CD11b mediates hypertensive cardiac remodeling by regulating macrophage infiltration and polarization
Copyright © 2023. Production and hosting by Elsevier B.V..
INTRODUCTION: Leukocyte infiltration is an early event during cardiac remodeling frequently leading to heart failure (HF). Integrins mediate leukocyte infiltration during inflammation. However, the importance of specific integrins in hypertensive cardiac remodeling is still unclear.
OBJECTIVES: To elucidate the significance of CD11b in hypertensive cardiac remodeling.
METHODS: Angiotensin (Ang II) or deoxycorticosterone acetate (DOCA)-salt was used to induce cardiac remodeling in mice of gene knockout (KO), bone marrow (BM) chimera, and the CD11b neutralizing antibody or agonist leukadherin-1 (LA1) treatment.
RESULTS: Our microarray data showed that integrin subunits Itgam (CD11b) and Itgb2 (CD18) were the most highly upregulated in Ang II-infused hearts. CD11b expression and CD11b/CD18+ myelomonocytes were also time-dependently increased. KO or pharmacological blockade of CD11b greatly attenuated cardiac remodeling and macrophage infiltration and M1 polarization induced by Ang II or DOCA-salt. This protection was verified in wild-type mice transplanted with CD11b-deficient BM cells. Conversely, administration of CD11b agonist LA1 showed the opposite effects. Further, CD11b KO reduced Ang II-induced macrophage adhesion and M1 polarization, leading to reduction of cardiomyocyte enlargement and fibroblast differentiation in vitro. The numbers of CD14+CD11b+CD18+ monocytes and CD15+CD11b+CD18+ granulocytes were obviously higher in HF patients than in normal controls.
CONCLUSION: Our data demonstrate an important role of CD11b+ myeloid cells in hypertensive cardiac remodeling, and suggest that HF may benefit from targeting CD11b.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:55 |
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| Enthalten in: |
Journal of advanced research - 55(2024) vom: 19. Jan., Seite 17-31 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yun-Long [VerfasserIn] |
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| Links: |
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| Themen: |
6E0A168OB8 |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 08.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jare.2023.02.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353286338 |
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| 500 | |a Date Revised 08.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Production and hosting by Elsevier B.V. | ||
| 520 | |a INTRODUCTION: Leukocyte infiltration is an early event during cardiac remodeling frequently leading to heart failure (HF). Integrins mediate leukocyte infiltration during inflammation. However, the importance of specific integrins in hypertensive cardiac remodeling is still unclear | ||
| 520 | |a OBJECTIVES: To elucidate the significance of CD11b in hypertensive cardiac remodeling | ||
| 520 | |a METHODS: Angiotensin (Ang II) or deoxycorticosterone acetate (DOCA)-salt was used to induce cardiac remodeling in mice of gene knockout (KO), bone marrow (BM) chimera, and the CD11b neutralizing antibody or agonist leukadherin-1 (LA1) treatment | ||
| 520 | |a RESULTS: Our microarray data showed that integrin subunits Itgam (CD11b) and Itgb2 (CD18) were the most highly upregulated in Ang II-infused hearts. CD11b expression and CD11b/CD18+ myelomonocytes were also time-dependently increased. KO or pharmacological blockade of CD11b greatly attenuated cardiac remodeling and macrophage infiltration and M1 polarization induced by Ang II or DOCA-salt. This protection was verified in wild-type mice transplanted with CD11b-deficient BM cells. Conversely, administration of CD11b agonist LA1 showed the opposite effects. Further, CD11b KO reduced Ang II-induced macrophage adhesion and M1 polarization, leading to reduction of cardiomyocyte enlargement and fibroblast differentiation in vitro. The numbers of CD14+CD11b+CD18+ monocytes and CD15+CD11b+CD18+ granulocytes were obviously higher in HF patients than in normal controls | ||
| 520 | |a CONCLUSION: Our data demonstrate an important role of CD11b+ myeloid cells in hypertensive cardiac remodeling, and suggest that HF may benefit from targeting CD11b | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cardiac remodeling | |
| 650 | 4 | |a Hypertensive stimuli | |
| 650 | 4 | |a Integrin CD11b | |
| 650 | 4 | |a Macrophage infiltration and polarization | |
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| 700 | 1 | |a Yu, Wei-Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Qiu-Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui-Hua |e verfasserin |4 aut | |
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