Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E-deficient mice

T Hayek, J Attias, J Smith, JL Breslow… - Journal of …, 1998 - journals.lww.com
T Hayek, J Attias, J Smith, JL Breslow, S Keidar
Journal of cardiovascular pharmacology, 1998journals.lww.com
The effect of the angiotensin-converting enzyme (ACE) inhibitor, captopril, on the
development of atherosclerosis was determined in the apolipoprotein (apo) E-deficient mice.
These mice develop severe hypercholesterolemia and extensive atherosclerotic lesions on
chow diet, similar to those found in humans. Furthermore, in these mice, accelerated
atherosclerosis is associated with increased plasma lipid peroxidation, a phenomenon that
may play a crucial role in the buildup of the atherosclerotic lesions. Mice received either …
Abstract
The effect of the angiotensin-converting enzyme (ACE) inhibitor, captopril, on the development of atherosclerosis was determined in the apolipoprotein (apo) E-deficient mice. These mice develop severe hypercholesterolemia and extensive atherosclerotic lesions on chow diet, similar to those found in humans. Furthermore, in these mice, accelerated atherosclerosis is associated with increased plasma lipid peroxidation, a phenomenon that may play a crucial role in the buildup of the atherosclerotic lesions. Mice received either placebo or 50 mg/kg/day of captopril. After 12 weeks of treatment, captopril reduced the aortic-lesion area by 70% compared with that of the placebo-treated group. Captopril also increased the resistance of low-density lipoprotein (LDL) to CuSO 4-induced oxidative stress, as shown by a significant reduction in the LDL content of malondialdehyde (MDA) by 30%, as well as by the prolongation of the lag time required for LDL oxidation from 55 min in the placebo-treated mice to 70 min in the captopril-treated mice, and reduction of the maximum LDL oxidation at 150 min by 35%. In vitro studies demonstrated that preincubation of LDL with captopril, inhibited the onset of CuSO 4-induced LDL peroxidation up to 120 min, and reduced the LDL content of MDA by 90%. We conclude that captopril attenuates atherosclerosis in the apo E-deficient mice, and this phenomenon may be related to its inhibitory effect on the plasma LDL oxidation.
Lippincott Williams & Wilkins