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Altered composition and functional profile of high-density lipoprotein in leprosy patients.
PLOS Neglected Tropical Diseases ( IF 3.8 ) Pub Date : 2020-03-30 , DOI: 10.1371/journal.pntd.0008138
Robertha Mariana R Lemes 1 , Carlos Adriano de M E Silva 2 , Maria Ângela de M Marques 2 , Georgia C Atella 3 , José Augusto da C Nery 4 , Maria Renata S Nogueira 5 , Patricia S Rosa 5 , Cléverson T Soares 5 , Prithwiraj De 2 , Delphi Chatterjee 2 , Maria Cristina V Pessolani 1 , Cristiana S de Macedo 1, 6
Affiliation  

The changes in host lipid metabolism during leprosy have been correlated to fatty acid alterations in serum and with high-density lipoprotein (HDL) dysfunctionality. This is most evident in multibacillary leprosy patients (Mb), who present an accumulation of host lipids in Schwann cells and macrophages. This accumulation in host peripheral tissues should be withdrawn by HDL, but it is unclear why this lipoprotein from Mb patients loses this function. To investigate HDL metabolism changes during the course of leprosy, HDL composition and functionality of Mb, Pb patients (paucibacillary) pre- or post-multidrug therapy (MDT) and HC (healthy controls) were analyzed. Mb pre-MDT patients presented lower levels of HDL-cholesterol compared to HC. Moreover, Ultra Performance Liquid Chromatography-Mass Spectrometry lipidomics of HDL showed an altered lipid profile of Mb pre-MDT compared to HC and Pb patients. In functional tests, HDL from Mb pre-MDT patients showed impaired anti-inflammatory and anti-oxidative stress activities and a lower cholesterol acceptor capacity compared to other groups. Mb pre-MDT showed lower concentrations of ApoA-I (apolipoprotein A-I), the major HDL protein, when compared to HC, with a post-MDT recovery. Changes in ApoA-I expression could also be observed in M. leprae-infected hepatic cells. The presence of bacilli in the liver of a Mb patient, along with cell damage, indicated hepatic involvement during leprosy, which may reflect on ApoA-I expression. Together, altered compositional and functional profiles observed on HDL of Mb patients can explain metabolic and physiological changes observed in Mb leprosy, contributing to a better understanding of its pathogenesis.

中文翻译:

麻风病患者高密度脂蛋白的组成和功能谱发生改变。

麻风病期间宿主脂质代谢的变化与血清中脂肪酸的改变和高密度脂蛋白(HDL)功能障碍相关。这在多菌性麻风病患者 (Mb) 中最为明显,其在雪旺细胞和巨噬细胞中存在宿主脂质的积累。HDL 可以消除宿主外周组织中的这种积累,但尚不清楚为什么来自 Mb 患者的这种脂蛋白会失去这种功能。为了研究麻风病过程中 HDL 代谢的变化,对多药治疗 (MDT) 前后 Mb、Pb 患者(少杆菌)和 HC(健康对照)的 HDL 组成和功能进行了分析。与 HC 相比,MDT 前 Mb 患者的 HDL 胆固醇水平较低。此外,HDL 的超高效液相色谱-质谱脂质组学显示,与 HC 和 Pb 患者相比,MDT 前 Mb 的脂质谱发生了改变。在功能测试中,与其他组相比,MDT 前 Mb 患者的 HDL 显示出抗炎和抗氧化应激活性受损,胆固醇受体能力较低。与 HC 相比,MDT 前的 Mb 显示 ApoA-I(载脂蛋白 AI)(主要 HDL 蛋白)浓度较低,且 MDT 后恢复。在麻风分枝杆菌感染的肝细胞中也可以观察到 ApoA-I 表达的变化。Mb 患者肝脏中存在杆菌以及细胞损伤,表明麻风病期间肝脏受累,这可能反映在 ApoA-I 表达上。总之,在 Mb 患者 HDL 上观察到的组成和功能谱的改变可以解释在 Mb 麻风病中观察到的代谢和生理变化,有助于更好地了解其发病机制。
更新日期:2020-03-30
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