Journal
HUMAN GENE THERAPY
Volume 29, Issue 12, Pages 1387-1395Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2016.144
Keywords
ACE2; aneurysm; inflammation; MMP
Categories
Funding
- National 973 Basic Research Program of China [2013CB530700]
- National Natural Science Foundation of China [81570729, 81170207]
- Shandong Provincial Science Foundation of China [81170207, 03BS37]
- Program of State Chinese Medicine Administration Bureau [JDZX2012113]
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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.
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