Altered high-density lipoprotein composition and functions during severe COVID-19.
Altered high-density lipoprotein composition and functions during severe COVID-19.
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DOI：
10.1038/s41598-021-81638-1
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发表时间：
2021-01-27
影响因子：
4.6
通讯作者：
Meilhac O
中科院分区：
文献类型：
--
作者：
Begue F;Tanaka S;Mouktadi Z;Rondeau P;Veeren B;Diotel N;Tran-Dinh A;Robert T;Vélia E;Mavingui P;Lagrange-Xélot M;Montravers P;Couret D;Meilhac O
2019冠状病毒病（COVID-19）大流行正在影响全球数百万患者。最初接触SARS-CoV-2的后果不仅仅是肺损伤，特别是对脂质代谢的影响。据报道，COVID-19患者的HDL-C水平降低。由于HDL颗粒显示出抗氧化、抗炎和潜在的抗感染特性，我们旨在表征COVID-19期间相对于健康受试者的HDL蛋白质组和功能。从8名重症COVID-19患者在D3和D 7入住重症监护室（第1天，D1）时采样的血浆中以及16名性别和年龄匹配的健康受试者中分离HDL。通过LC-MS/MS进行蛋白质组学分析。比较COVID-19和对照之间HDL中鉴定的蛋白质的相对量。蛋白质印迹分析证实，与对照组相比，COVID-19患者的载脂蛋白A-I和对氧磷酶1含量较低，而血清淀粉样蛋白A和α-1抗胰蛋白酶含量较高。患者HDL对TNFα刺激的内皮细胞（通透性、VE-钙粘蛋白紊乱和凋亡）的保护作用较弱。在这些条件下，相对于对照组，COVID-19中HDL对细胞凋亡的抑制作用减弱。总之，我们发现了严重COVID-19患者HDL蛋白质组的重大变化和功能性下降。
Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
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