高密度脂蛋白受体SR-BI纯合子无效突变和载脂蛋白E基因低脂饲养的鼠病理学情况与人类CHD动脉粥样硬化相同。高胆固醇血症，闭塞性冠状动脉粥样硬化，心肌梗死，心功能不全（心脏扩大、心脏收缩功能减退，射血分数降低，心电图异常）和提前死亡（平均年龄6周）。还表现为阻碍RBC的成熟和未全部脂化的血浆胆固醇比率（0.8），以及相关的脂蛋白形态异常。使用降脂、抗动脉粥样硬化和抗氧化的普罗布考可将患者寿命延长60周（平均36周）。控制普罗布考给药和停药时间可控制死亡的发生并表明重要的病理变化经常发生在未经治疗的大约3到5周的双基因敲除鼠，普罗布考可延缓即使在发生严重的CHD情况下也可延缓心衰。

    Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): 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 approximately 3 (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.