Abstract W P79: Hyperhomocysteinemia Is Associated With Vulnerability of the Cerebral Aneurysmal Wall to Rupture in Ovariectomized Rats
Introduction: The pathogenesis of cerebral aneurysms is multifactorial. Hyperhomocysteinemia (HHcy) leads to endothelial and platelet deterioration and may be associated with the formation of cerebral aneurysms. We tested the hypothesis that HHcy plays a role in the growth and/or rupture of cerebral aneurysms.
Methods: We exposed 13-week-old female Sprague-Dawley rats fed a high-salt diet to estrogen deficiency, hemodynamic stress, and induced hypertension. To induce HHcy we added methionine to their drinking water.
Results: In methionine induced rats the aneurysms the total rupture rate was higher than in rats not treated with methionine. One fourth of the aneurysms arising at the anterior communicating (Acom) artery, and half of the aneurysms at the posterior half of the circle of Willis, but no aneurysms at the anterior cerebral artery-olfactory artery (ACA-OA) bifurcation ruptured. Immunohistochemically, the infiltration of M1 macrophages was increased at the Acom artery in methionine induced rats and the messenger ribonucleic acid level of matrix metalloproteinase (MMP)-9, the ratio of MMP-9 to tissue inhibitor of metalloprotease (TIMP)2, and the interleukin-6 level were higher at the Acom artery than the ACA-OA bifurcation. Treatment with folic acid abolished the exacerbated effects due to HHcy, suggesting that the propensity of cerebral aneurysms at the Acom artery to rupture is attributable to disequilibrium between the degradation molecules and their inhibitors and to macrophage infiltration.
Conclusion: HHcy may be associated with vulnerability of the cerebral aneurysmal wall to rupture in hypertensive ovariectomized rats.
Author Disclosures: M. Korai: None.
- © 2015 by American Heart Association, Inc.