Gender‐Specific Cardiovascular Advantages In Apolipoprotein E Knockout Mice and Effects Of Captopril Treatment On Late‐Stage Atherosclerotic Lesion Progression

Abstract

Apolipoprotein E‐deficient (apoE KO) mice develop aortic lesions when fed a high fat (Western) diet. Reports suggest that pre‐menopausal females are protected from adverse cardiovascular events brought on by an increase in circulating lipids. We hypothesized that there is gender‐afforded cardiovascular protection in apoE KO mice with established atherosclerotic lesions. Six‐week old apoE KO mice were fed a Western diet for 14 weeks and received 450 mg/ml collagen/100μM epinephrine (7.5 ml/kg, i.v.) at 20 weeks to assess cardiac risk. Some mice received captopril (25 mg/kg/day) for weeks 18–20. Western‐fed apoE KO mice had higher serum cholesterol levels (males 843.4 ± 40.7, females 991.6 ± 85.5 mg/dl) compared with chow‐fed wild‐type mice (WT, males 132.1 ± 4.5, females 95.6 ± 10.7 mg/dl, both p<0.01) and elevated aortic COX‐2 expression. Lesions were greater in Western‐fed apoE KO mice than in chow‐fed mice (males 20.50 ± 0.82 vs 3.38 ± 0.19%, females 20.57 ± 1.12 vs 3.29 ± 0.15%; both p<0.01), and were reduced in male (59.9%, p<0.01) and female (50.1%, p<0.01) captopril‐treated mice. Apo E KO females fed a Western diet had a higher survival percentage than their male counterparts. We conclude that cardiovascular protection is conferred on pre‐menopausal apoE KO female mice and that two weeks of captopril significantly reduces late‐stage atherosclerotic lesions in male and female apoE KO mice.