Published Online
on August 11, 2003

A more recent version of this article appeared on August 19, 2003

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Submitted on January 3, 2003
Revised on June 30, 2003
Accepted on July 2, 2003

Role of a Decreased Expression of the Local Renin-Angiotensin System in the Etiology of Cerebral Aneurysms

Hiroki Ohkuma MD^*, Shigeharu Suzuki MD, Seiichiroh Fujita MD, and Wataru Nakamura MD

Department of Neurosurgery, Hirosaki University, Hirosaki (H.O., S.S., S.F.), and Department of Neurosurgery, Kuroishi Municipal Hospital, Kuroishi (H.O., W.N.), Japan.

^* To whom correspondence should be addressed. E-mail: ohkuma{at}cc.hirosaki-u.ac.jp.

Background--Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated.

Methods and Results--The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT₁) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT₁ receptor, and angiotensin II in the aneurysmal wall.

Conclusion--Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.

Key words: aneurysm • angiotensin • arteries

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