This Article Full Text Full Text (PDF) Data Supplement Data Supplement All Versions of this Article: 116/24/2830    most recent CIRCULATIONAHA.107.728303v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Aoki, T. Articles by Hashimoto, N. PubMed PubMed Citation Articles by Aoki, T. Articles by Hashimoto, N. Pubmed/NCBI databases Substance via MeSH Related Collections Other Vascular biology Animal models of human disease Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Related Article

(Circulation. 2007;116:2830-2840.)
© 2007 American Heart Association, Inc.

Stroke

NF-B Is a Key Mediator of Cerebral Aneurysm Formation

Tomohiro Aoki, MD; Hiroharu Kataoka, MD, PhD; Munehisa Shimamura, MD, PhD; Hironori Nakagami, MD, PhD; Kouji Wakayama, MD; Takuya Moriwaki, MD, PhD; Ryota Ishibashi, MD; Kazuhiko Nozaki, MD, PhD; Ryuichi Morishita, MD, PhD; Nobuo Hashimoto, MD, PhD

From the Department of Neurosurgery, Kyoto University, Graduate School of Medicine, Kyoto (T.A., H.K., T.M., R.I., K.N., N.H.); Department of Advanced Clinical Science and Therapeutics, Tokyo University, Graduate School of Medicine, Tokyo (M.S., K.W.); and Department of Clinical Gene Therapy, Osaka University, Graduate School of Medicine, Osaka (H.N., R.M.), Japan.

Correspondence to Hiroharu Kataoka, MD, PhD, Department of Neurosurgery, Kyoto University, Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606–8507, Japan. E-mail kataoka{at}kuhp.kyoto-u.ac.jp

Received July 17, 2007; accepted October 9, 2007.

Background— Subarachnoid hemorrhage caused by the rupture of cerebral aneurysm (CA) remains a life-threatening disease despite recent diagnostic and therapeutic advancements. Recent studies strongly suggest the active participation of macrophage-mediated chronic inflammatory response in the pathogenesis of CA. We examined the role of nuclear factor-B (NF-B) in the pathogenesis of CA formation in this study.

Methods and Results— In experimentally induced CAs in rats, NF-B was activated in cerebral arterial walls in the early stage of aneurysm formation with upregulated expression of downstream genes. NF-B p50 subunit–deficient mice showed a decreased incidence of CA formation with less macrophage infiltration into the arterial wall. NF-B decoy oligodeoxynucleotide also prevented CA formation when it was administered at the early stage of aneurysm formation in rats. Macrophage infiltration and expression of downstream genes were dramatically inhibited by NF-B decoy oligodeoxynucleotide. In human CA walls, NF-B also was activated, especially in the intima.

Conclusions— Our data indicate that NF-B plays a crucial role as a key regulator in the initiation of CA development by inducing some inflammatory genes related to macrophage recruitment and activation. NF-B may represent a therapeutic target of a novel medical treatment for CA.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2007 116: 2773. [Full Text]