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Late‐Stage Captopril Treatment Reduces Atherosclerotic Lesion Progression in Apolipoprotein E Knockout Mice
Author(s) -
Procknow Jesse David,
Sprague Randy,
Stephenson Alan H.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.593.19
Subject(s) - captopril , apolipoprotein e , endocrinology , medicine , lesion , apolipoprotein b , cholesterol , angiotensin converting enzyme , pathology , blood pressure , disease
C57BL6 mice in which the gene for apolipoprotein E is deleted (apoE KO) develop significant lesions in the area of the proximal aorta when fed a high fat diet. It was previously reported that apoE KO mice treated with captopril, an angiotensin converting enzyme (ACE) inhibitor, had reduced late stage atherosclerotic lesions after 12 weeks when compared to untreated mice. We wished to determine the effect of captopril on atherosclerotic lesions in a similar model using a shorter timeframe to more closely represent ACE inhibitor use in humans. 6‐week old apoE KO mice were fed a high‐fat (Western) diet for 14 weeks with captopril (25 mg/kg/day) in their drinking water for weeks 12‐14. At 20‐weeks of age, mice were sacrificed and blood was collected via heart puncture. Aortas were fixed and stained with oil red O to visualize lesions. Serum cholesterol levels were higher in Western‐fed apoE KO mice (males 843.41 ± 40.72, females 991.63 ± 85.57 mg/dl) compared to chow‐fed wild‐type mice (control) (males 132.07 ± 4.50, females 95.60 ± 10.74 mg/dl, both p<0.01). Lesions were greater in Western‐fed apoE KO mice versus control 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. We conclude that two weeks of captopril treatment significantly reduces late‐stage atherosclerotic lesions in apoE knockout mice.