國家衛生研究院 NHRI:Item 3990099045/9992
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    題名: Heme oxygenase-1 deficiency exacerbates angiotensin II-induced aortic aneurysm in mice
    作者: Ho, YC;Wu, ML;Gung, PY;Chen, CH;Kuo, CC;Yet, SF
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Abdominal aortic aneurysm (AAA) is a chronic but often fatal disease in elderly population. Heme oxygenase-1 (HO-1) is a stress response protein with antioxidative and anti-inflammatory properties. HO-1 has been shown to protect against atherogenesis and arterial intimal thickening. Emerging evidences suggest that AAA and arterial occlusive disease have distinct pathogenic mechanisms. Thus, in this study we investigated the role of HO-1 in angiotensin II-induced AAA formation in HO-1+/+apoE-/- and HO-1-/-apoE-/- mice. We found that complete loss of HO-1 increased AAA incidence and rupture rate, and drastically increased aneurysmal area and severity, accompanied with severe elastin degradation and medial degeneration. Interestingly, we often observed not only AAA but also thoracic aortic aneurysm in HO-1-/-apoE-/- mice. Furthermore, reactive oxygen species levels, vascular smooth muscle cell (VSMC) loss, macrophage infiltration, matrix metalloproteinase (MMP) activity were markedly enhanced in the aneurysmal aortic wall in HO-1-/-apoE-/- mice. In addition, HO-1-/-apoE-/- VSMCs were more susceptible to oxidant-induced cell death and macrophages from HO-1-/-apoE-/- mice had aggravated responses to angiotensin II with substantial increases in inflammatory cytokine productions and MMP9 activity. Taken together, our results demonstrate the essential roles of HO-1 in suppressing the pathogenesis of AAA. Targeting HO-1 might be a promising therapeutic strategy for AAA.
    日期: 2016-09-08
    關聯: Oncotarget. 2016 Sep 8;7(42):67760-67776.
    Link to: http://dx.doi.org/10.18632/oncotarget.11917
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000387446800006
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85022321372
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