Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings
Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings
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DOI：
10.1194/jlr.s120000720
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发表时间：
2020-08-01
影响因子：
6.5
通讯作者：
Retterstol, Kjetil
中科院分区：
文献类型：
--
作者：
Norum, Kaare R.;Remaley, Alan T.;Retterstol, Kjetil
LCAT在胆固醇逆向转运过程中将游离胆固醇转化为胆固醇酯。家族性LCAT缺乏症（FLD）是一种遗传性疾病，由Kaare R. Norum和Egil Gjone，1967年。这份报告是2017年研讨会的总结，Norum博士在会上讲述了FLD的历史，LCAT的主要专家分享了他们的研究结果。Tesmer实验室分享了LCAT和其同源物溶酶体磷脂酶A2的结构发现。报告了芬兰、巴西、挪威和意大利的FLD患者研究结果，以及患者登记的状态。Kuivenhoven和Calabresi博士提供了来自基因突变携带者的数据，表明FLD不一定会加速动脉粥样硬化。Ng博士分享说，LCAT基因敲除小鼠可以免受饮食诱导的肥胖、胰岛素抵抗和非酒精性脂肪肝疾病的影响。Zhou博士介绍了用于治疗目的的增加LCAT活性的多种创新，而Remaley博士展示了用重组人LCAT（rhLCAT）治疗FLD患者的结果。Karathanasis博士表明，小鼠中的rhLCAT输注刺激胆固醇流出，并表明它还可以增强巨噬细胞的胆固醇流出。虽然LCAT在动脉粥样硬化中的作用仍然难以捉摸，但共识是，对酶和疾病的持续研究将为心脏病和FLD患者带来更好的治疗。
LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.