Human gene therapy · 2018
Angiotensin-Converting Enzyme 2 Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hao QingQing, Dong XueFei, Chen Xu, Yan Feng, Wang Xiaoyu, Shi HaiShui, Dong Bo
Аннотация
Recent studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, few studies have reported the direct effect of ACE2 overexpression on the aneurysm. This study hypothesized that the overexpression of ACE2 may prevent the pathogenesis of aneurysms by decreasing RAS activation. Thirty-nine mice were randomly assigned to three groups (n = 13 in each group): the Ad.ACE2 group, the Ad.EGFP group, and a control group. After 8 weeks of treatment, abdominal aortas with AAAs were obtained for hematoxylin and eosin staining, Verhoeff Van Gieson staining, immunohistochemistry, and Western blotting. The incidence and severity of AAAs, macrophage infiltration, and MMP protein expression were all recorded. The results showed that ACE2 gene transfer significantly decreased the occurrence of AAAs and inhibited AAA formation in ApoE-/- mice by inhibiting the inflammatory response and MMP activation, and the mechanisms may involve decreased ERK and Ang II-nuclear factor kappa B signaling pathways.
Предметные рубрики MeSH
AdenoviridaeAngiotensin IIAngiotensin-Converting Enzyme 2AnimalsAorta, AbdominalAortic Aneurysm, AbdominalApolipoproteins EBlotting, WesternDisease Models, AnimalGene Expression RegulationGenetic VectorsGreen Fluorescent ProteinsHumansImmunohistochemistryMacrophagesMaleMatrix Metalloproteinase 13MiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NF-kappa BPeptidyl-Dipeptidase ASignal Transduction