Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.
Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.
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DOI：
10.3390/cells12151938
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发表时间：
2023-07-26
期刊：
影响因子：
6
通讯作者：
Sorgi, Carlos A.
中科院分区：
文献类型：
--
作者：
Toro, Diana Mota V.;da Silva-Neto, Pedro V.;de Carvalho, Jonatan C. S. A.;Fuzo, Carlos A. M.;Perez, Malena M.;Pimentel, Vinicius E.;Fraga-Silva, Thais F. C.;Oliveira, Camilla N. S. R.;Caruso, Glaucia R.;Vilela, Adriana F. L.;Nobre-Azevedo, Pedro V.;Defelippo-Felippe, Thiago V.;Argolo, Jamille G. M. M.;Degiovani, Augusto M.;Ostini, Fatima M. R.;Feitosa, Marley R. S.;Parra, Rogerio S. C.;Vilar, Fernando C. G.;Gaspar, Gilberto G.;da Rocha, Jose J. R.;Feres, Omar P.;Costa, Gabriel P.;Maruyama, Sandra R. C.;Russo, Elisa M. S.;Fernandes, Ana Paula M.;Santos, Isabel K. F. M.;Malheiro, Adriana T.;Sadikot, Ruxana T.;Bonato, Vania L. D.;Cardoso, Cristina R. B.;Dias-Baruffi, Marcelo;Trape, Atila A.;Faccioli, Lucia H. A.;Sorgi, Carlos A.
SARS-CoV-2感染触发了不同的疾病发展模式，其特征是宿主调控反应的显著变化。严重病例表现为严重的肺部炎症和全身反应。值得注意的是，危重病人表现出一种“脂质风暴”，影响炎症过程和组织损伤。鞘磷脂(SLS)在多种细胞和组织过程中发挥着关键作用，包括炎症、代谢紊乱和癌症。在这项研究中，我们使用高分辨率质谱仪研究了来自正常对照组(n=55)、新冠肺炎患者(n=204)和恢复期患者(n=77)的血浆中SL的代谢。这些数据与与新冠肺炎临床严重程度相关的炎症参数相关。此外，我们利用RNAseq分析来检测SL途径中涉及的酶的基因表达。我们的分析显示，研究参与者的血浆中存在来自7个家族的38个SL物种。在患有严重疾病的患者中，观察到SL物种图谱中最深刻的变化。值得注意的是，一种主要的鞘磷脂(SM D18：1)物种作为新冠肺炎严重性的潜在生物标志物出现，显示恢复期个体血浆中的水平下降。SM水平升高与年龄、住院时间、临床评分、中性粒细胞计数以及IL-6和IL-8的产生呈正相关。有趣的是，我们确定了SM(D18：1/24：0)介导的对疾病严重性的假定保护作用，而神经酰胺(Cer)物种(D18：1/24：1)和(D18：1/24：0)与风险增加相关。此外，我们观察到严重新冠肺炎患者血细胞中参与SL途径的关键酶表达增强，提示在SM合成的同时，主要流向Cer的生成。这些发现强调了SM作为新冠肺炎预后生物标记物的潜力，并强调了有前景的药理靶点。通过靶向鞘脂通路，可能会出现新的治疗策略，以减轻新冠肺炎的严重程度并改善患者预后。
SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a “lipid storm”, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.
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影响因子：
4.6
作者：
Janneh AH;Kassir MF;Dwyer CJ;Chakraborty P;Pierce JS;Flume PA;Li H;Nadig SN;Mehrotra S;Ogretmen B
通讯作者：
Ogretmen B
影响因子：
4.6
作者：
Ghidoni R;Caretti A;Signorelli P
通讯作者：
Signorelli P
脂质筏参与SARS-COV进入Vero E6细胞。
DOI：
10.1016/j.bbrc.2008.02.023
发表时间：
2008-05-02
影响因子：
3.1
作者：
Lu Y;Liu DX;Tam JP
通讯作者：
Tam JP
DOI：
10.1038/nrm.2017.107
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Hannun YA;Obeid LM
通讯作者：
Obeid LM
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J