High density lipoprotein: are elevated levels desirable and achievable?
High density lipoprotein: are elevated levels desirable and achievable?
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高密度脂蛋白：升高的水平是否理想且可以实现？
DOI：
10.2174/138161280401221007110721
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发表时间：
1970
影响因子：
3.1
通讯作者：
M. Pape
中科院分区：
文献类型：
--
作者：
C. Bisgaier;M. Pape
在这篇综述中，我们重点讨论了两个与高密度脂蛋白有关的问题。首先，升高的高密度脂蛋白水平是否是理想的临床血浆终点；其次，如果是这样，能否设计出策略，允许识别升高高密度脂蛋白的药物。为了回答第一个问题，我们简要回顾了人类流行病学和前瞻性数据，这些数据表明高密度脂蛋白是冠心病(CHD)的危险因素。为了介绍提高高密度脂蛋白的策略，我们接下来简要回顾高密度脂蛋白的结构和酶特性，然后讨论目前关于脂蛋白代谢起源的想法。然后，通过分析来自人类突变的数据、具有改变高密度脂蛋白代谢的基因工程动物模型和体外实验系统，我们转向涉及高密度脂蛋白的合成、分解代谢和重塑的关键血浆和细胞相关蛋白的讨论。最后，我们提出了提高高密度脂蛋白的方法，这些方法要么是基于对有机小分子的鉴定，要么是更多的非常规方法，如基因治疗或生物制剂进入血浆。这最后一节是基于对新旧两种高密度脂蛋白升高化合物的假定作用机制的评估。我们的综述总结了一种乐观的观点，即可以找到在治疗人类低脂蛋白血症和冠心病方面有希望的药物。
In this review we focus on addressing two questions concerning high density lipoproteins (HDL). First, are elevated levels of HDL a desirable clinical plasma endpoint and secondly, if so, can strategies be devised that would allow the identification of agents to elevate HDL. To address the first question we briefly review the human epidemiologic and prospective data that identifies HDL as a risk factor for coronary heart disease (CHD). To introduce HDL elevating strategies, we next provide a brief review of the structural and enzymatic features of HDL followed by a discussion on the current thinking of the metabolic origin of the lipoprotein. We then turn to discussions on the key plasma and cell associated proteins involved in the synthesis, catabolism, and remodeling of HDL by analyzing data derived from human mutations, genetically engineered animal models with altered HDL metabolism and in vitro experimental systems. Lastly, we propose approaches to raise HDL that are either based on identification of small organic molecules or more unconventional approaches such as gene therapy or delivery of biologicals into plasma. This last section is based on an evaluation of the putative mechanism of actions of both old and new HDL elevating compounds. Our review concludes with an optimistic view that agents can be identified which may have promise in the treatment of human hypoalphalipoproteinemia and CHD.