Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model.

Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Research Abstract Details 

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Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Abstract Text:

Takashi Miyake,Motokuni Aoki,Hisao Masaki,Tomio Kawasaki,Masako Oishi,Kazusaburo Kataoka,Toshio Ogihara,Yasufumi Kaneda,Ryuichi Morishita,Takashi Miyake,Motokuni Aoki,Hisao Masaki,Tomio Kawasaki,Masako Oishi,Kazusaburo Kataoka,Toshio Ogihara,Yasufumi Kaneda,Ryuichi Morishita,

Because current therapy to treat abdominal aortic aneurysm (AAA), and particularly to manage small AAA, is limited to elective surgical repair, we explored less invasive molecular therapy by simultaneous inhibition of the transcription factors nuclear factor (NF)kappaB and ets using a decoy strategy. Both NFkappaB and ets were shown to be markedly activated in human AAA. In addition, NFkappaB- and ets-positive cells were increased in the aneurysm wall, and a part of the expression of NFkappaB and ets was detected in migrating macrophages. Thus, we used chimeric decoy oligodeoxynucleotides (ODNs) containing consensus sequences of both NFkappaB and ets binding sites to treat AAA. Inhibitory effects of chimeric decoy ODNs on matrix metalloproteinase-1 and -9 expression were confirmed by ex vivo experiments using a human aorta organ culture. To examine the regressive effect in a rabbit already-formed AAA model, transfection by wrapping a delivery sheet containing chimeric decoy ODNs around the aneurysm was performed 1 week after incubation with elastase. Importantly, treatment with chimeric decoy ODNs significantly decreased the size of AAA. Interestingly, significant preservation of elastic fibers was observed with chimeric decoy ODN treatment, accompanied by a reduction of matrix metalloproteinase-2 and -9 and induction of macrophage apoptosis. Regression of AAA was also associated with an increase in elastin and collagen type I and III synthesis in the aneurysm wall. Minimally invasive molecular therapy targeted to the inhibition of NFkappaB and ets is expected to be useful for AAA through the rebalance of matrix synthesis and degradation.

Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Publishing Authors By Initials

T Miyake,M Aoki,H Masaki,T Kawasaki,M Oishi,K Kataoka,T Ogihara,Y Kaneda,R Morishita,T Miyake,M Aoki,H Masaki,T Kawasaki,M Oishi,K Kataoka,T Ogihara,Y Kaneda,R Morishita,

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Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Circulation research

VOLUME: 101

Page Numbers: 1175-84

Journal Abbreviation: Circ. Res.

ISSN: 1524-4571

DAY: 20

MONTH: 09

YEAR: 2007

Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. Information

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LANGUAGE: eng

NlmUniqueID: 47103

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Grant and Affiliation Information for Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model.

AFFILIATION: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.

Country: United States

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MEDLINETA: Circ Res

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