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Subarachnoid hemorrhage due to rupture of intracranial aneurysms is a life-threatening disease. Although some previous reports have demonstrated an association between lipid accumulation and degenerative changes in aneurysmal walls in humans, epidemiological studies have failed to identify dyslipidemia as a risk factor for intracranial aneurysms. Thus, we examined whether an increase in serum cholesterol levels facilitates the progression of intracranial aneurysms in a rat model. Rats were given a high-fat diet (HFD) and subjected to an intracranial aneurysm model. The HFD elevated their serum cholesterol levels. The intracranial aneurysms induced at the anterior cerebral artery-olfactory artery bifurcation were significantly larger in the high-fat group than in the normal-chow group. Histological analysis demonstrated that the loss of medial smooth muscle layers was exacerbated in the high-fat group and indicated the presence of macrophage-derived foam cells in the lesions. In in vitro experiments, the expression levels of the pro-inflammatory genes induced by LPS in RAW264.7-derived foam cells were significantly higher than those in RAW264.7 cells. The combination of these results suggests that increased serum cholesterol levels facilitate degenerative changes in the media and the progression of intracranial aneurysms presumably through foam cell transformation.

High-Fat Diet Intake Promotes the Enlargement and Degenerative Changes in the Media of Intracranial Aneurysms in Rats