Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization.

Abstract

OBJECTIVE:

We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA).

METHODS:

AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations.

RESULTS:

Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p<0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p<0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p<0.05).

CONCLUSION:

Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA.

• Authors: Hidehiro Kaneko, Toshihisa Anzai, Maho Morisawa, Takashi Kohno, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Masayuki Shimoda, Aya Sasaki, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Kazuo Tsubota, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
• Journal: Atherosclerosis (Atherosclerosis) Vol. 217 Issue 2 Pg. 350-7 (Aug 2011) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 21530968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Anti-Inflammatory Agents
• Antioxidants
• Inflammation Mediators
• Reactive Oxygen Species
• Rela protein, mouse
• Stilbenes
• Transcription Factor RelA
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse
• Calcium Chloride
• Resveratrol

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Aorta, Abdominal (drug effects, immunology, metabolism, pathology)
• Aortic Aneurysm, Abdominal (chemically induced, immunology, metabolism, pathology, physiopathology, prevention & control)
• Calcium Chloride
• Disease Models, Animal
• Extracellular Matrix (metabolism)
• Inflammation (chemically induced, immunology, metabolism, physiopathology, prevention & control)
• Inflammation Mediators (metabolism)
• Macrophages (drug effects, immunology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred C57BL
• Neovascularization, Physiologic (drug effects)
• Oxidative Stress (drug effects)
• Phosphorylation
• Reactive Oxygen Species (metabolism)
• Resveratrol
• Stilbenes (pharmacology)
• Transcription Factor RelA (metabolism)