Adventitial recruitment of Lyve-1− macrophages drives aortic aneurysm in an angiotensin-2-based murine model
| Autor: | 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 |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Clinical Science. 135:1295-1309 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|