Abstract 13663: Resveratrol Inhibits Development of Abdominal Aortic Aneurysm through Attenuation of Inflammation, Oxidative Stress, and Neovascularization
Objective: Abdominal aortic aneurysm (AAA) is pathologically characterized by chronic inflammation, increased oxidative stress, and neovascularization in aortic wall. Resveratrol is one of the polyphenols and known to attenuate inflammation, oxidative stress, and pathological angiogenesis.
Methods and Results: AAA was induced in male C57/BLJ6 mice at the age of 6 weeks by periaortic application of CaCl2. NaCl (0.9%) was substituted for CaCl2 in sham-operated mice. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=8 for each) or resveratrol at the doses of 100mg/kg every day (AAA/CON, AAA/RSVT, n=8 for each). Six weeks after the operation, aortic diameter was enlarged in AAA/CON compared with Sham/CON (p< 0.01). Treatment with resveratrol reduced aneurism size (1.3 ± 0.1 vs. 0.9 ± 0.1 mm, p< 0.05) in association with reduced inflammatory cells infiltration into the aortic wall compared with AAA/CON. Elastica von Gieson staining showed destructed wavy morphology of the elastic lamellae in AAA/CON was preserved in AAA/RSVT. Treatment with resveratrol reduced mRNA expression of MCP-1 and TNF-α compared with AAA/CON (−90%, −58%, respectively, both p< 0.05). Immunoblotting showed expression of p-JNK and TNF-α was upregulated in AAA/CON compared with sham operated group. They were reduced in AAA/RSVT. Compared with AAA/CON, AAA/RSVT showed reduced mRNA expression of p47, glutathione peroxidase (GPX)-1 and GPX-3 (−72%, −63%, and −81%, respectively, all p< 0.01). Increased 8-hydroxy-2′-deoxyguanosine positive cell count in AAA was reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was also reduced in AAA/RSVT compared with AAA/CON (both p< 0.05). Compared with AAA/CON, Mac-3+ monocytes/macrophages and CD31+ vessels in aortic wall were decreased in AAA/RSVT (4.5±0.6 vs. 1.5±0.6/HPF, 3.6±1.1 vs. 0.6±0.5/HPF, respectively, both p< 0.05).
Conclusions: Treatment with resveratrol in mice prevented AAA development, in association with reduced infiltration of inflammatory cells, oxidative stress and MMPs activity, preserved ECM structure, and neoangiogenesis. These findings suggest a therapeutic potential of resveratrol for AAA.
- © 2010 by American Heart Association, Inc.