Role of a decreased expression of the local renin-angiotensin system in the etiology of cerebral aneurysms.
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.


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.


CONCLUSIONS
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.
Ohkuma
Hiroki
H
Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562 Japan. ohkuma@cc.hirosaki-u.ac.jp
Suzuki
Shigeharu
S
Fujita
Seiichiroh
S
Nakamura
Wataru
W
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism / Q000502:physiology / Q000601:surgery; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008055:Lipids / Q000097:blood; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics; D012083:Renin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D008055:Lipids; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019715:Tissue Inhibitor of Metalloproteinase-1; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D012083:Renin