TY - JOUR
T1 - Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization
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
N1 - Funding Information:
This study was supported by the Medical School Faculty and an Alumni Grant from the Keio University Medical Science Fund (to T.A.) and the grant from the Ministry of Health, Labor and Welfare (Research Group of Intractable Vasculitis) Japan (to Y.O.).
PY - 2011/8
Y1 - 2011/8
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.
AB - 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.
KW - Abdominal aortic aneurysm
KW - Extracellular matrix
KW - Inflammation
KW - Neoangiogenesis
KW - Oxidative stress
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U2 - 10.1016/j.atherosclerosis.2011.03.042
DO - 10.1016/j.atherosclerosis.2011.03.042
M3 - Article
C2 - 21530968
AN - SCOPUS:79960698213
VL - 217
SP - 350
EP - 357
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 2
ER -