| First Author | Adam M | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 8 | Pages | 1796-1805 |
| PubMed ID | 29880489 | Mgi Jnum | J:285115 |
| Mgi Id | MGI:6385420 | Doi | 10.1161/ATVBAHA.117.310672 |
| Citation | Adam M, et al. (2018) Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm. Arterioscler Thromb Vasc Biol 38(8):1796-1805 |
| abstractText | Objective- Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Approach and Results- Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE(-/-) infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1+/-10.8% (control) to 131.0+/-5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4(+)/CD25(+)/Foxp3 (forkhead box P3)(+) regulatory T cells, with fewer CD8(+)/GZMB(+) (granzyme B) cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-alpha (tumor necrosis factor-alpha), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of lipopolysaccharide-stimulated and Ang II-primed human peripheral blood mononuclear cells. Conclusions- Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression. |
