Hayek T, Attias J, Smith J, Breslow J L, Keidar S
The Lipid Research Laboratory, Rambam Medical Center, Technion Faculty of Medicine and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
J Cardiovasc Pharmacol. 1998 Apr;31(4):540-4. doi: 10.1097/00005344-199804000-00011.
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 CuSO4-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 CuSO4-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.
在载脂蛋白E缺乏的小鼠中，研究了血管紧张素转换酶（ACE）抑制剂卡托普利对动脉粥样硬化发展的影响。这些小鼠在普通饮食条件下会出现严重的高胆固醇血症和广泛的动脉粥样硬化病变，与人类的情况相似。此外，在这些小鼠中，动脉粥样硬化的加速发展与血浆脂质过氧化增加有关，这一现象可能在动脉粥样硬化病变的形成中起关键作用。小鼠分别接受安慰剂或50mg/kg/天的卡托普利治疗。治疗12周后，与安慰剂治疗组相比，卡托普利使主动脉病变面积减少了70%。卡托普利还增加了低密度脂蛋白（LDL）对硫酸铜诱导的氧化应激的抵抗力，表现为LDL中丙二醛（MDA）含量显著降低30%，同时LDL氧化所需的延迟时间从安慰剂治疗小鼠的55分钟延长至卡托普利治疗小鼠的70分钟，并且在150分钟时最大LDL氧化降低了35%。体外研究表明，LDL与卡托普利预孵育可抑制硫酸铜诱导的LDL过氧化达120分钟，并使LDL中MDA含量降低90%。我们得出结论，卡托普利可减轻载脂蛋白E缺乏小鼠的动脉粥样硬化，这一现象可能与其对血浆LDL氧化的抑制作用有关。
