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(Hypertension. 2006;48:628.)
© 2006 American Heart Association, Inc.

Original Articles

Hypertension Accelerated Experimental Abdominal Aortic Aneurysm Through Upregulation of Nuclear Factor B and Ets

Suguru Shiraya; Ken Miwa; Motokuni Aoki; Takashi Miyake; Masako Oishi; Kazusaburo Kataoka; Shigetsugu Ohgi; Toshio Ogihara; Yasufumi Kaneda; Ryuichi Morishita

From the Division of Clinical Gene Therapy (S.S., K.M., T.M., R.M.), Department of Geriatric Medicine (M.A., T.O.), and Division of Gene Therapy Science (Y.K.), Graduate School of Medicine, Osaka University, Suita, Japan; Second Department of Surgery (S.S., K.M., S.O.), Faculty of Medicine, Tottori University, Yonago, Japan; and the Department of Pharmacy (M.O., K.K.), Osaka University Hospital, Osaka, Japan.

Correspondence to Ryuichi Morishita, Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail morishit{at}cgt.med.osaka-u.ac.jp

In this study, we focused on the effect of hypertension on the transcription factors nuclear factor B (NFB) and ets in the mechanisms of abdominal aortic aneurysm (AAA), and we investigated how hypertension affects the progression of AAA. AAA was produced by elastase perfusion in hypertensive rats and normotensive rats. The size of AAA rapidly increased in hypertensive rats as compared with normotensive rats. Western blot analysis demonstrated that the expression of matrix metalloproteinase (MMP)-2, -3 , -9, and -12, as well as intercellular adhesion molecule, was increased in hypertensive AAA rats, accompanied by upregulation of NFB and ets. Moreover, in situ zymography showed that the activity of MMPs was increased in the aorta of a hypertensive AAA model as compared with that in a normotensive AAA model. Interestingly, transfection of chimeric decoy oligodeoxynucleotide (ODN) resulted in significant inhibition of aortic dilatation both in normotensive and hypertensive rats at 4 weeks after transfection. Destruction of elastic fibers was also significantly inhibited by transfection of chimeric decoy ODN in both hypertensive rats and normotensive rats. The expression of MMP-2, -3, -9, and -12, as well as intercellular adhesion molecule, was significantly attenuated by the chimeric decoy ODN, accompanied by inhibition of the migration of macrophages. Also, the effect of chimeric decoy ODN was confirmed in an organ culture. The present study demonstrated that hypertension accelerated the progression of experimental AAA through upregulation of NFB and ets. Inhibition of NFB and ets could be a novel therapeutic strategy to treat AAA in hypertensive patients.

Key Words: abdominal aortic aneurysm • hypertension • NFB • ets • decoy • MMP

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