Association of cardiometabolic microRNAs with COVID-19 severity and mortality.
Association of cardiometabolic microRNAs with COVID-19 severity and mortality.
复制标题
心脏代谢microRNA与COVID-19严重程度和死亡率的相关性
DOI：
10.1093/cvr/cvab338
复制
发表时间：
2022-01-29
影响因子：
10.8
通讯作者：
Mayr M
中科院分区：
文献类型：
--
作者：
Gutmann C;Khamina K;Theofilatos K;Diendorfer AB;Burnap SA;Nabeebaccus A;Fish M;McPhail MJW;O'Gallagher K;Schmidt LE;Cassel C;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Roy R;Edgeworth JD;Shah AM;Hayday AC;Traby L;Hackl M;Eichinger S;Shankar-Hari M;Mayr M
2019冠状病毒病（COVID-19）可导致多器官损伤。血液中的MicroRNAs （miRNAs）反映细胞活化和组织损伤。我们旨在确定循环mirna与COVID-19严重程度和28天重症监护病房（ICU）死亡率的关系。我们对健康对照（n = 11）、非重度（n = 18）和重度（n = 18） COVID-19患者的血浆进行了RNA-Seq检测，并根据细胞和组织来源选择了14种mirna，通过逆转录定量聚合酶链反应（RT-qPCR）在轻度（n = 6）、中度（n = 39）和重度（n = 16）患者的单独队列中进行检测。然后对ICU COVID-19患者的纵向样本（n = 240个样本，n = 65例）进行RT-qPCR检测。共有60种mirna，包括血小板、内皮细胞、肝细胞和心肌细胞来源的mirna，根据严重程度差异表达，miR-133a升高和miR-122降低也与28天死亡率相关。我们利用基于质谱的蛋白质组学数据来获取相应的蛋白质轨迹。肌细胞源性（myomiR） miR-133a与中性粒细胞计数呈负相关，与中性粒细胞脱粒相关蛋白（如髓过氧化物酶）呈正相关。相反，肝细胞来源的miR-122水平与肝脏参数以及肝来源的急性期阳性（负相关）和阴性蛋白（正相关）相关。最后，我们将mirna与COVID-19严重程度和结局的既定标志物（即SARS-CoV-2 rnai、年龄、BMI、d -二聚体和肌钙蛋白）进行比较。虽然RNAemia、年龄和肌钙蛋白是更好的死亡率预测因子，但miR-133a和miR-122在严重程度上表现出更好的分类性能。在二联体和三联体组合中，mirna改善了已建立的严重程度和死亡率标记物的分类性能。不同组织来源的循环mirna，包括几种已知的心脏代谢生物标志物，随着COVID-19严重程度的增加而上升。MyomiR miR-133a和肝脏来源的miR-122也与28天死亡率有关。MiR-133a反映炎症诱导的心肌细胞损伤，而miR-122反映肝脏急性期反应。
Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.
登录
查看更多内容
影响因子：
6.6
作者：
Gutmann, Clemens;Joshi, Abhishek;Mayr, Manuel
通讯作者：
Mayr, Manuel
DOI：
10.1074/mcp.ra120.002305
发表时间：
2021
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Burnap SA;Mayr U;Shankar-Hari M;Cuello F;Thomas MR;Shah AM;Sabroe I;Storey RF;Mayr M
通讯作者：
Mayr M
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
24
作者：
Heslop, Claire L.;Frohlich, Jiri J.;Hill, John S.
通讯作者：
Hill, John S.
影响因子：
4.8
作者：
Fu, XY;Kassim, SY;Heinecke, JW
通讯作者：
Heinecke, JW