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首例重组高密度脂蛋白颗粒用于重症监护病房(ICU)的新冠肺炎患者:一项多组学探索性研究

First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation.

作者信息

Tanaka Sébastien, Begue Floran, Veeren Bryan, Tran-Dinh Alexy, Robert Tiphaine, Tashk Parvine, Lortat-Jacob Brice, Faille Dorothée, de Chaisemartin Luc, Zappella Nathalie, Atchade Enora, Kramer Laura, Montravers Philippe, Meilhac Olivier

机构信息

AP-HP, Service d'Anesthésie-Réanimation, CHU Bichat-Claude Bernard, 75018 Paris, France.

INSERM, UMR 1188 Diabète Athérothombose Réunion Océan Indien (DéTROI), Université de La Réunion, 97400 Saint-Denis, France.

出版信息

Biomedicines. 2022 Mar 23;10(4):754. doi: 10.3390/biomedicines10040754.

Abstract

High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.

摘要

高密度脂蛋白(HDL)具有多种内皮保护特性。在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染期间,高密度脂蛋白胆固醇(HDL-C)浓度显著降低,并且研究已描述了HDL颗粒功能的严重受损。在此,我们报告了对一名重症监护病房的重症2019冠状病毒病(COVID-19)患者首次给予重组HDL(rHDL)颗粒的多组学研究。每次注射重组HDL后,血浆载脂蛋白A1(ApoA1)升高而HDL-C降低,这表明这些颗粒在逆向胆固醇转运方面发挥了作用。注射重组HDL后,大HDL颗粒的比例也增加。对通过超速离心分离的HDL进行鸟枪法蛋白质组学分析表明,注射后ApoA1更为丰富,而鉴定出的大多数促炎蛋白含量较少。对血清淀粉样蛋白A-1、炎症标志物和细胞因子的评估显示,在重组HDL输注期间,其中大多数显著下降。我们的结果表明,重组HDL输注是可行的,并且是一种在COVID-19患者中有待探索的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b34/9029957/fba4e0867cdd/biomedicines-10-00754-g001.jpg

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