Academic Journal
Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice
| العنوان: | Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice |
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| المؤلفون: | Wan, Wuzhou, Lionakis, Michail S., Liu, Qian, Roffê, Ester, Murphy, Philip M. |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2013 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Vascular biology and angiogenesis |
| الوصف: | Aims Recent evidence suggests that both Ccr7 and its ligands, Ccl19 and Ccl21, are present in mouse and human atherosclerotic plaques; however, the role of Ccr7 in atherogenesis is still controversial. Here, we addressed this question by using the classic apolipoprotein E-deficient ( ApoE−/− ) mouse model of atherosclerosis. Methods and results Ccr7−/−ApoE−/− double knockout mice and Ccr7+/+ApoE−/− littermates were generated and maintained on a high-fat Western diet for 8 weeks to induce atherosclerosis. Ccr7−/−ApoE−/− mice showed an ∼80% increase in atherosclerotic lesion size in the whole aorta and a two-fold increase in the aortic root compared with Ccr7+/+ApoE−/− mice. Ccr7−/−ApoE−/− mice had increased T cells in the blood, bone marrow, and spleen, as well as in atherosclerotic lesions. Competitive repopulation experiments revealed that T cells from Ccr7−/−ApoE−/− mice migrated poorly into lymph nodes but better into mouse aortas compared with T cells from Ccr7+/+ApoE−/− mice. Transplantation of the bone marrow from Ccr7−/−ApoE−/− mice into lethally irradiated Ccr7+/+ApoE−/− mice resulted in ∼60% more atherosclerotic lesions compared with Ccr7+/+ApoE−/− donor bone marrow, suggesting that exacerbation was mediated by a Ccr7+ bone marrow-derived cell(s). Furthermore, in Ccr7−/−ApoE−/− mice the serum level of IL-12 was markedly increased, whereas the level of transforming growth factor beta (TGF-β) was significantly decreased, suggesting an imbalance of T cell responses in these mice. Conclusion Our data suggest that genetic deletion of Ccr7 exacerbates atherosclerosis by increasing T cell accumulation in atherosclerotic lesions. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://cardiovascres.oxfordjournals.org/cgi/content/short/97/3/580; http://dx.doi.org/10.1093/cvr/cvs349 |
| DOI: | 10.1093/cvr/cvs349 |
| الاتاحة: | http://cardiovascres.oxfordjournals.org/cgi/content/short/97/3/580 https://doi.org/10.1093/cvr/cvs349 |
| Rights: | Copyright (C) 2013, European Society of Cardiology |
| رقم الانضمام: | edsbas.DAA0ACBD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cvr/cvs349 |
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