Abdominal aortic aneurysms (AAAs) are a chronic inflammatory vascular disease for which pharmacological treatments are not available. Gadd153 is closely associated with the onset of vascular smooth muscle cells (VSMCs) apoptosis. However, a role for Gadd153 in AngII-induced AAA formation is currently unknown. In our study, lentiviral-mediated silencing of Gadd153 through small RNA interference was performed in mice, which was further used for the establishment of mouse experimental AAA induced by infusion of angiotensin II (AngII). We found that Gadd153 deficiency prevented AngII-induced AAA formation in mice 14 days post perfusion compared with wild-type control mice. Moreover, Gadd153 deficiency significantly reduced lesion macrophage and CD4+ T-cell content, T-cell proliferation, SMC apoptosis, and matrix metalloproteinase expression. In vitro studies revealed that Gadd153 deficiency regulated microvessel growth and monocyte migration. In addition, Gadd153 deficiency also affected AAA lesion Mac-3 macrophage accumulation or CD31 microvessel numbers. In conclusion, our study demonstrates that Gadd153 plays an essential role in AngII-induced AAA formation by promoting inflammatory cells proliferation and vascular SMC apoptosis affecting MMPs expression.
Keywords: Gadd153; abdominal aortic aneurysms; angiotensin II; matrix metalloproteinases.
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