Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
Departments of Medicine (Cardiology) and Cell Biology and the Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, New York, NY 10016, United States.
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Jul;1863(7):762-771. doi: 10.1016/j.bbalip.2018.03.010. Epub 2018 Apr 6.
Understanding the molecular defects underlying cardiovascular disease is necessary for the development of therapeutics. The most common method to lower circulating lipids, which reduces the incidence of cardiovascular disease, is statins, but other drugs are now entering the clinic, some of which have been approved. Nevertheless, patients cannot tolerate some of these therapeutics, the drugs are costly, and/or the treatments are approved for only rare forms of disease. Efforts to find alternative treatments have focused on other factors, such as apolipoproteinB (apoB), which transports cholesterol in the blood stream. The levels of apoB are regulated by endoplasmic reticulum (ER) associated degradation as well as by a post ER degradation pathway in model systems, and we suggest that these events provide novel therapeutic targets. We discuss first how cardiovascular disease arises and how cholesterol is regulated, and then summarize the mechanisms of action of existing treatments for cardiovascular disease. We then review the apoB biosynthetic pathway, focusing on steps that might be amenable to therapeutic interventions.
了解心血管疾病的分子缺陷对于治疗方法的发展是必要的。降低心血管疾病发病率的最常见方法是他汀类药物，但现在其他药物也已进入临床，其中一些已获得批准。然而，有些患者无法耐受这些治疗药物，这些药物成本高昂，或者这些治疗方法仅适用于罕见的疾病形式。寻找替代治疗方法的努力集中在其他因素上，例如载脂蛋白 B (apoB)，它在血液中运输胆固醇。apoB 的水平受到内质网 (ER) 相关降解以及模型系统中 ER 后降解途径的调节，我们认为这些事件提供了新的治疗靶点。我们首先讨论了心血管疾病的发生方式以及胆固醇的调节方式，然后总结了现有心血管疾病治疗方法的作用机制。然后，我们回顾了 apoB 的生物合成途径，重点介绍了可能适合治疗干预的步骤。
