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

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

Research output: Contribution to journalArticle

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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 (100mg/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.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalAtherosclerosis
Volume217
Issue number2
DOIs
Publication statusPublished - 2011 Aug

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Abdominal Aortic Aneurysm
Oxidative Stress
Inflammation
resveratrol
Cell Count
Therapeutics
Stilbenes
Chemokine CCL2
Matrix Metalloproteinase 2
Rubber
Matrix Metalloproteinase 9
Phytochemicals
Intercellular Adhesion Molecule-1
Intraperitoneal Injections
Cell Size
Vascular Endothelial Growth Factor A
Aneurysm
Extracellular Matrix

Keywords

  • Abdominal aortic aneurysm
  • Extracellular matrix
  • Inflammation
  • Neoangiogenesis
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization. / Kaneko, Hidehiro; Anzai, Toshihisa; Morisawa, Maho; Kohno, Takashi; Nagai, Toshiyuki; Anzai, Atsushi; Takahashi, Toshiyuki; Shimoda, Masayuki; Sasaki, Aya; Maekawa, Yuichiro; Yoshimura, Koichi; Aoki, Hiroki; Tsubota, Kazuo; Yoshikawa, Tsutomu; Okada, Yasunori; Ogawa, Satoshi; Fukuda, Keiichi.

In: Atherosclerosis, Vol. 217, No. 2, 08.2011, p. 350-357.

Research output: Contribution to journalArticle

Kaneko, H, Anzai, T, Morisawa, M, Kohno, T, Nagai, T, Anzai, A, Takahashi, T, Shimoda, M, Sasaki, A, Maekawa, Y, Yoshimura, K, Aoki, H, Tsubota, K, Yoshikawa, T, Okada, Y, Ogawa, S & Fukuda, K 2011, 'Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization', Atherosclerosis, vol. 217, no. 2, pp. 350-357. https://doi.org/10.1016/j.atherosclerosis.2011.03.042
Kaneko, Hidehiro ; Anzai, Toshihisa ; Morisawa, Maho ; Kohno, Takashi ; Nagai, Toshiyuki ; Anzai, Atsushi ; Takahashi, Toshiyuki ; Shimoda, Masayuki ; Sasaki, Aya ; Maekawa, Yuichiro ; Yoshimura, Koichi ; Aoki, Hiroki ; Tsubota, Kazuo ; Yoshikawa, Tsutomu ; Okada, Yasunori ; Ogawa, Satoshi ; Fukuda, Keiichi. / Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization. In: Atherosclerosis. 2011 ; Vol. 217, No. 2. pp. 350-357.
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AU - Kaneko, Hidehiro

AU - Anzai, Toshihisa

AU - Morisawa, Maho

AU - Kohno, Takashi

AU - Nagai, Toshiyuki

AU - Anzai, Atsushi

AU - Takahashi, Toshiyuki

AU - Shimoda, Masayuki

AU - Sasaki, Aya

AU - Maekawa, Yuichiro

AU - Yoshimura, Koichi

AU - Aoki, Hiroki

AU - Tsubota, Kazuo

AU - Yoshikawa, Tsutomu

AU - Okada, Yasunori

AU - Ogawa, Satoshi

AU - Fukuda, Keiichi

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N2 - 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 (100mg/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.

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