Effects of Atorvastatin on the Induction of Experimental Cerebral Aneurysm in a High Lipid Diet Rat Model

Lim, Jeong Kyu; Yeo, In Sung; Yi, Jin Seok; Lee, Hyung Jin; Yang, Ji Ho; Lee, Il Woo

Abstract

OBJECTIVE
Previously, we reported that a high lipid diet significantly increases the induction rate of cerebral aneurysm (CA) formation in an experimentally induced CA rat model, suggesting that hypercholesterolemia with chronic inflammation leads to aneurysm formation. To elucidate the role of hypercholesterolemia in CA formation, experimentally induced CA was evaluated in rats fed a high lipid diet and treated with low and high doses of atorvastatin.
METHODS
Thirty-seven, 7-week-old male Sprague-Dawley rats underwent a CA induction procedure. The control animals (n = 11) were fed a normal diet, and the experimental animals (n = 26) were fed a diet containing high lipid content for 3 months. The experimental group comprised a high-dose atorvastatin group (20 mg/kg/day, n = 15) and low-dose atorvastatin group (1 mg/kg/day, n = 11). Three months after the operation, induction of CA formation in the three groups was analyzed.
RESULTS
Induced CA formation was 67%, 63%, and 36% in the control, high lipid/high atovastatin, and high lipid/low atovastatin group, respectively. The differences resulting from high-dose and low-dose atorvastatin were significant (Pearson k2, P = 0.028 and 0.029, respectively).
CONCLUSIONS
A high lipid diet can significantly increase induction of CA formation. However, the lack of decreased induction in atorvastatin-treated animals suggests that high and low doses of atorvastatin do not inhibit the potential effects of hypercholesterolemia on CA formation. Further studies, such as those utilizing apolipoprotein E knockout mice, are necessary to elucidate the exact role of hypercholesterolemia in the pathophysiology of CA.