...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse
【24h】

Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

机译：普罗布考可预防高密度脂蛋白受体SR-BI /载脂蛋白E双敲除小鼠的早期冠心病和死亡

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type 1) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHID): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5-6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between approximate to3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. [References: 62]
机译：低脂饮食喂养的高密度脂蛋白受体SR-BI（B类清道夫受体1型）和载脂蛋白E基因具有纯合无效突变的小鼠表现出与人类动脉粥样硬化性冠心病（CHID）共同的病理征象：高胆固醇血症，闭塞性冠状动脉粥样硬化，心肌梗塞，心脏功能障碍（心脏肿大，收缩功能和射血分数降低以及ECG异常）和过早死亡（平均年龄6周）。它们还显示出RBC的成熟受阻和血浆未酯化/总胆固醇之比异常高（0.8），并伴有异常的脂蛋白形态异常（片状/囊泡状和堆积盘状颗粒使人联想到卵磷脂/胆固醇酰基转移酶缺乏症和胆汁淤积症）。降脂，抗动脉粥样硬化和抗氧化药物普罗布考的治疗可延长寿命长达60周（平均36周），在5-6周龄时，实际上可以完全逆转心脏和大多数RBC的病变，并纠正未酯化的总胆固醇比（0.3）和相关的异常脂蛋白异常形态。普罗布考的给药和撤药时间的控制可以控制死亡的发作，并表明关键的病理变化通常发生在大约3岁（断奶）至5周龄的未经治疗的双基因敲除小鼠中，即使普罗布考发生后，普罗布考也可延迟心力衰竭。大量冠心病。普罗布考治疗调节双基因敲除小鼠的病理生理学的能力增强了这种鼠类系统用于分析冠心病的病理生理学和预防和治疗心血管疾病的新方法的临床前测试的潜力。 [参考：62]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号