The Potential Role of CXCL5 on Acute Aortic Dissection
| Autor: | Ling-Yu Liao, 廖羚羽 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Acute aortic dissection (AAD) is an acute inflammatory vascular disease with increasing incidence on morbidity and mortality. AAD formation begins with the sudden intimal tear, which allows pulsatile blood to enter the media and cause medial layer separation termed false lumen. The acute dilation creates a thin, inflamed, and extremely fragile outer aortic wall and causes sudden death by dissection. Acute dissections are those less than 14 days’ duration from the onset of symptoms. Beyond 14 days after onset, dissections are considered chronic phase. Early diagnosis and treatments are critical to aortic dissection. However, the direct cellular and molecular mechanisms in AAD are unknown. Angiotensin II-stimulated neutrophils had been demonstrated to initiate AAD by infiltrating to the aortic intima. Depletion of neutrophils had been elucidated to attenuate AAD incidence. Therefore, neutrophils become important in AAD formation. The CXC chemokines of CXC-motif chemokine 5 (CXCL5), also called epithelial cell-derived neutrophil-activation peptide (ENA-78), has been known to attract and activate neutrophils. As a result, CXCL5 may have an important role in AAD formation. In this study, we established the animal model by angiotensin II infusion for 3 days after the lysyl oxidase inhibitor beta-aminopropionitrile(BAPN) treatment for 4 weeks in 4 week-old male BALB/c mice. In our model, AAD was developed in 100% of cases, and approximately 31% of the mice died before sacrifice. In different time point of our model, the morphology indicated that angiotensin II triggered AAD formation. In western blot assay, CXCL5 expression was increased after treatment with angiotensin II. Also we found that vascular smooth muscle cells and neutrophils might be the source of CXCL5. In depletion of CXCL5, there were significant decreased the severe of AAD in ultrasound, aorta wet weight and en face assay. Histology of CXCL5 showed treatment with antibody had decreased the expression. Moreover, matrix metalloproteinase 9 (MMP9) was present in treatment with BAPN 4 week, and increased after angiotensin II infusion. Immunohistochemistry of neutrophil indicated that angiotensin II triggered neutrophil infiltrated into media layer and attenuated by anti-CXCL5 antibody. To conclusion, CXCL5 could retard the progression of AAD, and be a potential treatment target for AAD. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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