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• W4362657603 abstract "Background: Abdominal aortic aneurysm (AAA) is a potentially lethal disease that lacks pharmacological treatment. Degradation of extracellular matrix proteins, especially elastin laminae, is the hallmark for AAA development. DOCK2 (dedicator of cytokinesis 2) has shown proinflammatory effects in several inflammatory diseases and acts as a novel mediator for vascular remodeling. However, the role of DOCK2 in AAA formation remains unknown. Methods: Ang II (angiotensin II) infusion of ApoE −/− (apolipoprotein E deficient) mouse and topical elastase-induced AAA combined with DOCK2 −/− (DOCK2 knockout) mouse models were used to study DOCK2 function in AAA formation/dissection. The relevance of DOCK2 to human AAA was examined using human aneurysm specimens. Elastin fragmentation in AAA lesion was observed by elastin staining. Elastin-degrading enzyme MMP (matrix metalloproteinase) activity was measured by in situ zymography. Results: DOCK2 was robustly upregulated in AAA lesion of Ang II–infused ApoE −/− mice, elastase-treated mice, as well as human AAA lesions. DOCK2 −/− significantly attenuated the Ang II–induced AAA formation/dissection or rupture in mice along with reduction of MCP-1 (monocyte chemoattractant protein-1) and MMP expression and activity. Accordingly, the elastin fragmentation observed in ApoE −/− mouse aorta infused with Ang II and elastase-treated aorta was significantly attenuated by DOCK2 deficiency. Moreover, DOCK2 −/− decreased the prevalence and severity of aneurysm formation, as well as the elastin degradation observed in the topical elastase model. Conclusions: Our results indicate that DOCK2 is a novel regulator for AAA formation. DOCK2 regulates AAA development by promoting MCP-1 and MMP2 expression to incite vascular inflammation and elastin degradation." @default.
• W4362657603 created "2023-04-07" @default.
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• W4362657603 date "2023-06-01" @default.
• W4362657603 modified "2023-09-30" @default.
• W4362657603 title "DOCK2 Deficiency Attenuates Abdominal Aortic Aneurysm Formation—Brief Report" @default.
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• W4362657603 doi "https://doi.org/10.1161/atvbaha.122.318400" @default.
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