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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Augustin, Beulah Wu, Dongyuan Black, Lauren Page Bertrand, Andrew Sulaiman, Dawoud Hopson, Charlotte Jacob, Vinitha Shavit, Jordan A. Hofmaenner, Daniel A. Labilloy, Guillaume Smith, Leslie Cagmat, Emilio Graim, Kiley Datta, Susmita Reddy, Srinivasa T. Guirgis, Faheem W. |
| Abstract | Background Lipids play a critical role in defense against sepsis. We sought to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis. Methods Data from four adult sepsis studies were analyzed and findings were investigated in two external datasets. Previously characterized lipid dysregulation subphenotypes of hypolipoprotein (HYPO; low lipoproteins, increased mortality) and normolipoprotein (NORMO; higher lipoproteins, lower mortality) were studied. Leukocytes collected within 24 h of sepsis underwent RNA sequencing (RNAseq) and shotgun plasma lipidomics was performed. Results Of 288 included patients, 43% were HYPO and 57% were NORMO. HYPO patients exhibited higher median SOFA scores (9 vs 5, p = < 0.001), vasopressor use (67% vs 34%, p = < 0.001), and 28-day mortality (30% vs 16%, p = 0.004). Leukocyte RNAseq identified seven upregulated lipid metabolism genes in HYPO (PCSK9, DHCR7, LDLR, ALOX5, PLTP, FDFT1, and MSMO1) vs. NORMO patients. Lipidomics revealed lower cholesterol esters (CE, adjusted p = < 0.001), lysophosphatidylcholines (LPC, adjusted p = 0.001), and sphingomyelins (SM, adjusted p = < 0.001) in HYPO patients. In HYPO patients, DHCR7 expression strongly correlated with reductions in CE, LPC, and SM (p < 0.01), while PCSK9, MSMO1, DHCR7, PLTP, and LDLR upregulation were correlated with low LPC (p < 0.05). DHCR7, ALOX5, and LDLR correlated with reductions in SM (p < 0.05). Mortality and phenotype comparisons in two external datasets (N = 824 combined patients) corroborated six of the seven upregulated lipid genes (PCSK9, DHCR7, ALOX5, PLTP, LDLR, and MSMO1). Conclusion We identified a genetic lipid dysregulation signature characterized by seven lipid metabolism genes. Five genes in HYPO sepsis patients most strongly correlated with low CE, LPC, and SMs that mediate cholesterol storage and innate immunity. |
| Related Links | https://ccforum.biomedcentral.com/counter/pdf/10.1186/s13054-024-05216-3.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 13648535 |
| DOI | 10.1186/s13054-024-05216-3 |
| Journal | Critical Care |
| Issue Number | 1 |
| Volume Number | 28 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-12-24 |
| Access Restriction | Open |
| Subject Keyword | Intensive Critical Care Medicine Emergency Medicine Sepsis Cholesterol Lipids Phenotyping |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine |
| Journal Impact Factor | 8.8/2023 |
| 5-Year Journal Impact Factor | 10.4/2023 |
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