Adventitial recruitment of Lyve-1− macrophages drives aortic aneurysm in an angiotensin-2-based murine model
| العنوان: | Adventitial recruitment of Lyve-1− macrophages drives aortic aneurysm in an angiotensin-2-based murine model |
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| المؤلفون: | Shaun Pacheco, Thomas F. Lindsay, Yonghong Chen, Antigona Ulndreaj, Angela Li, Rickvinder Besla, John S Byrne, Myron I. Cybulsky, Marwan G Althagafi, Clinton S. Robbins |
| المصدر: | Clinical Science. 135:1295-1309 |
| بيانات النشر: | Portland Press Ltd., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pathology, medicine.medical_specialty, Inflammation, Pathogenesis, Mice, Aortic aneurysm, medicine.artery, medicine, Animals, Macrophage, Aorta, Abdominal, Aortic dissection, Aorta, biology, business.industry, Angiotensin II, Macrophages, Membrane Transport Proteins, General Medicine, medicine.disease, Abdominal aortic aneurysm, Aortic Aneurysm, Disease Models, Animal, cardiovascular system, biology.protein, Inflammation Mediators, medicine.symptom, business, Elastin, Aortic Aneurysm, Abdominal, Signal Transduction |
| الوصف: | Objective: Aortic macrophage accumulation is characteristic of the pathogenesis of abdominal aortic aneurysm (AAA) but the mechanisms of macrophage accumulation and their phenotype are poorly understood. Lymphatic vessel endothelial receptor-1 (Lyve-1+) resident aortic macrophages independently self-renew and are functionally distinct from monocyte-derived macrophages recruited during inflammation. We hypothesized that Lyve-1+ and Lyve-1− macrophages differentially contribute to aortic aneurysm. Approach and results: Angiotensin-2 and β-aminopropionitrile (AT2/BAPN) were administered to induce AAA in C57BL/6J mice. Using immunohistochemistry (IHC), we demonstrated primarily adventitial accumulation of aortic macrophages, and in association with areas of elastin fragmentation and aortic dissection. Compared with controls, AAA was associated with a relative percent depletion of Lyve-1+ resident aortic macrophages and accumulation of Lyve-1− macrophages. Using CD45.1/CD45.2 parabiosis, we demonstrated aortic macrophage recruitment in AAA. Depletion of aortic macrophages in CCR2−/− mice was associated with reduced aortic dilatation indicating the functional role of recruitment from the bone marrow. Depletion of aortic macrophages using anti-macrophage colony-stimulating factor 1 receptor (MCSF1R)-neutralizing antibody (Ab) reduced the incidence of AAA. Conditional depletion of Lyve-1+ aortic macrophages was achieved by generating Lyve-1wt/cre Csf1rfl/fl mice. Selective depletion of Lyve-1+ aortic macrophages had no protective effects following AT2/BAPN administration and resulted in increased aortic dilatation in the suprarenal aorta. Conclusions: Aortic macrophage accumulation in AAA derives from adventitial recruitment of Lyve-1− macrophages, with relative percent depletion of Lyve-1+ macrophages. Selective targeting of macrophage subtypes represents a potential novel therapeutic avenue for the medical treatment of AAA. |
| تدمد: | 1470-8736 0143-5221 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fae7807440bfb0c78e149e258894c691 https://doi.org/10.1042/cs20200963 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fae7807440bfb0c78e149e258894c691 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708736 01435221 |
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