Resolvin D1 decreases abdominal aortic aneurysm formation by inhibiting NETosis in a mouse model
| Autor: | Gorav Ailawadi, Michael Spinosa, Guanyi Lu, J. Michael Cullen, Michael S. Conte, Akshaya K. Meher, William G. Montgomery, Robert B. Hawkins, Anna Z. Fashandi, Ashish Sharma, Gang Su, Gilbert R. Upchurch, Morgan Salmon |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Docosahexaenoic Acids Mice Knockout ApoE Neutrophils medicine.medical_treatment Anti-Inflammatory Agents Inflammation Vascular Remodeling Extracellular Traps Histones 03 medical and health sciences Western blot Internal medicine Animals Medicine Aorta Abdominal Saline Pancreatic Elastase medicine.diagnostic_test business.industry Elastase Neutrophil extracellular traps medicine.disease Angiotensin II Abdominal aortic aneurysm Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Cytokine cardiovascular system Cytokines Matrix Metalloproteinase 2 Citrullination Surgery Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine business Aortic Aneurysm Abdominal |
| Zdroj: | Journal of Vascular Surgery. 68:93S-103S |
| ISSN: | 0741-5214 |
| Popis: | Objective Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. Methods Wild-type 8- to 12-week-old C57BL/6 male mice (n = 47) and apolipoprotein E-deficient (ApoE−/−) mice (n = 20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, wild-type mice were divided into three groups: a deactivated elastase control group, in which sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate-buffered saline (PBS) once a day until harvest; an elastase group, in which active elastase was used to induce AAA and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II)-induced AAA model, ApoE−/− mice were fed a high-fat diet and implanted with osmotic infusion pumps containing Ang II (1000 ng/kg/min). The Ang II model was divided into two groups: an Ang II control group, in which Ang II was delivered and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative day 3, day 14, or day 28, aortic and blood samples were collected for Western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. Results The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P Conclusions RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|