The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury
Abstract Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a stro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2017-12-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201707502 |
| _version_ | 1827059741650583552 |
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| author | Tobias Getzin Kashyap Krishnasamy Jaba Gamrekelashvili Tamar Kapanadze Anne Limbourg Christine Häger L Christian Napp Johann Bauersachs Hermann Haller Florian P Limbourg |
| author_facet | Tobias Getzin Kashyap Krishnasamy Jaba Gamrekelashvili Tamar Kapanadze Anne Limbourg Christine Häger L Christian Napp Johann Bauersachs Hermann Haller Florian P Limbourg |
| author_sort | Tobias Getzin |
| collection | DOAJ |
| description | Abstract Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a strong increase in endothelial proliferation, which is accompanied by induction of the chemokine CX3CL1 in endothelial cells near the wound edge, leading to progressive recruitment of Ly6Clo monocytes expressing high levels of the cognate CX3CR1 chemokine receptor. In Cx3cr1‐deficient mice recruitment of Ly6Clo monocytes, endothelial proliferation and regeneration of the endothelial monolayer after carotid injury are impaired, which is rescued by acute transfer of normal Ly6Clo monocytes. Furthermore, human non‐classical monocytes induce proliferation of endothelial cells in co‐culture experiments in a VEGFA‐dependent manner, and monocyte transfer following carotid injury promotes endothelial wound closure in a hybrid mouse model in vivo. Thus, CX3CR1 coordinates recruitment of specific monocyte subsets to sites of endothelial regeneration, which promote endothelial proliferation and arterial regeneration. |
| first_indexed | 2024-03-07T17:59:18Z |
| format | Article |
| id | doaj.art-02660350cd7d4fc89aacb5658d3e41e9 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T18:46:10Z |
| publishDate | 2017-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-02660350cd7d4fc89aacb5658d3e41e92024-10-20T11:39:52ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-12-0110215115910.15252/emmm.201707502The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injuryTobias Getzin0Kashyap Krishnasamy1Jaba Gamrekelashvili2Tamar Kapanadze3Anne Limbourg4Christine Häger5L Christian Napp6Johann Bauersachs7Hermann Haller8Florian P Limbourg9Vascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolDepartment of Cardiology and Angiology, Hannover Medical SchoolDepartment of Nephrology and Hypertension, Hannover Medical SchoolVascular Medicine Research, Hannover Medical SchoolAbstract Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a strong increase in endothelial proliferation, which is accompanied by induction of the chemokine CX3CL1 in endothelial cells near the wound edge, leading to progressive recruitment of Ly6Clo monocytes expressing high levels of the cognate CX3CR1 chemokine receptor. In Cx3cr1‐deficient mice recruitment of Ly6Clo monocytes, endothelial proliferation and regeneration of the endothelial monolayer after carotid injury are impaired, which is rescued by acute transfer of normal Ly6Clo monocytes. Furthermore, human non‐classical monocytes induce proliferation of endothelial cells in co‐culture experiments in a VEGFA‐dependent manner, and monocyte transfer following carotid injury promotes endothelial wound closure in a hybrid mouse model in vivo. Thus, CX3CR1 coordinates recruitment of specific monocyte subsets to sites of endothelial regeneration, which promote endothelial proliferation and arterial regeneration.https://doi.org/10.15252/emmm.201707502CX3CR1endothelial cellsmonocytesregenerationvascular injury |
| spellingShingle | Tobias Getzin Kashyap Krishnasamy Jaba Gamrekelashvili Tamar Kapanadze Anne Limbourg Christine Häger L Christian Napp Johann Bauersachs Hermann Haller Florian P Limbourg The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury EMBO Molecular Medicine CX3CR1 endothelial cells monocytes regeneration vascular injury |
| title | The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| title_full | The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| title_fullStr | The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| title_full_unstemmed | The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| title_short | The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| title_sort | chemokine receptor cx3cr1 coordinates monocyte recruitment and endothelial regeneration after arterial injury |
| topic | CX3CR1 endothelial cells monocytes regeneration vascular injury |
| url | https://doi.org/10.15252/emmm.201707502 |
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