卵磷脂：胆固醇酰基转移酶：从发现到最新发现的 50 年生物医学研究研讨会。,Journal of Lipid Research

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卵磷脂：胆固醇酰基转移酶：从发现到最新发现的 50 年生物医学研究研讨会。
Journal of Lipid Research ( IF 5.0 ) Pub Date : 2020-06-01 , DOI: 10.1194/jlr.s120000720
Kaare R Norum ₁ , Alan T Remaley ₂ , Helena E Miettinen ₃ , Erik H Strøm ₄ , Bruno E P Balbo ₅ , Carlos A T L Sampaio ₅ , Ingrid Wiig ₆ , Jan Albert Kuivenhoven ₇ , Laura Calabresi ₈ , John J Tesmer ₉ , Mingyue Zhou ₁₀ , Dominic S Ng ₁₁ , Bjørn Skeie ₁₂ , Sotirios K Karathanasis _{2,

13} , Kelly A Manthei ₁₄ , Kjetil Retterstøl _{15,

16}

Affiliation

Department of Nutrition, University of Oslo, Oslo, Norway.
National Institutes of Health, Bethesda, MD
Department of Medicine, University of Helsinki and University Central Hospital, Helsinki, Finland.
Departments of Pathology Oslo University Hospital, Oslo, Norway.
Division of Nephrology and Molecular Medicine Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Centre for Rare Disorders, Oslo University Hospital, Oslo, Norway.
Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Department of Biological Sciences, Purdue University, West Lafayette, IN.
Cardiometabolic Disorder Research, AMGEN, San Francisco, CA.
Department of Medicine, University of Toronto and Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
Anesthesiology, Oslo University Hospital, Oslo, Norway.
NeoProgen, Baltimore, MD.
Life Sciences Institute, University of Michigan, Ann Arbor, MI
Department of Nutrition, University of Oslo, Oslo, Norway
Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Lipid Clinic, Oslo University Hospital, Oslo, Norway.

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 于 1967 年首次描述。本报告是 2017 年研讨会的总结，Norum 博士讲述了 FLD 的历史，LCAT 的主要专家分享了他们的结果。Tesmer 实验室分享了 LCAT 和近同系物溶酶体磷脂酶 A2 的结构发现。介绍了芬兰、巴西、挪威和意大利对 FLD 患者的研究结果，以及患者登记的状态。博士 Kuivenhoven 和 Calabresi 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 博士分享了 LCAT-null 小鼠免受饮食引起的肥胖、胰岛素抵抗、和非酒精性脂肪肝。Zhou 博士提出了多项创新，用于增加 LCAT 活性以达到治疗目的，而 Remaley 博士则展示了用重组人 LCAT (rhLCAT) 治疗 FLD 患者的结果。Karathanasis 博士表明，在小鼠体内输注 rhLCAT 可刺激胆固醇流出，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。Karathanasis 表明，在小鼠体内输注 rhLCAT 会刺激胆固醇外流，并表明它还可以增强巨噬细胞的胆固醇外流。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。Karathanasis 表明，在小鼠体内输注 rhLCAT 会刺激胆固醇外流，并表明它还可以增强巨噬细胞的胆固醇外流。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。

"点击查看英文标题和摘要"

Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings.

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.

更新日期：2020-08-21

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