The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia
Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. However, it is not well understood what lipids are involved in the development of this condition, and even less is known how these lipids mediate its formation. To reveal the rela...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227521001000 |
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| author | Bing He Yu Liu Mano R. Maurya Paula Benny Cameron Lassiter Hui Li Shankar Subramaniam Lana X. Garmire |
| author_facet | Bing He Yu Liu Mano R. Maurya Paula Benny Cameron Lassiter Hui Li Shankar Subramaniam Lana X. Garmire |
| author_sort | Bing He |
| collection | DOAJ |
| description | Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. However, it is not well understood what lipids are involved in the development of this condition, and even less is known how these lipids mediate its formation. To reveal the relationship between lipids and preeclampsia, we conducted lipidomic profiling of maternal sera of 44 severe preeclamptic and 20 healthy pregnant women from a multiethnic cohort in Hawaii. Correlation network analysis showed that oxidized phospholipids have increased intercorrelations and connections in preeclampsia, whereas other lipids, including triacylglycerols, have reduced network correlations and connections. A total of 10 lipid species demonstrate significant changes uniquely associated with preeclampsia but not any other clinical confounders. These species are from the lipid classes of lysophosphatidylcholines, phosphatidylcholines (PCs), cholesteryl esters, phosphatidylethanolamines, lysophosphatidylethanolamines, and ceramides. A random forest classifier built on these lipids shows highly accurate and specific prediction (F1 statistic = 0.94; balanced accuracy = 0.88) of severe preeclampsia, demonstrating their potential as biomarkers for this condition. These lipid species are enriched in dysregulated biological pathways, including insulin signaling, immune response, and phospholipid metabolism. Moreover, causality inference shows that various PCs and lysophosphatidylcholines mediate severe preeclampsia through PC 35:1e. Our results suggest that the lipidome may play a role in the pathogenesis and serve as biomarkers of severe preeclampsia. |
| first_indexed | 2024-12-24T11:18:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T11:18:31Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-2b4b2cca1d1c463483f5b9ab7b1ba8a72022-12-21T16:58:18ZengElsevierJournal of Lipid Research0022-22752021-01-0162100118The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsiaBing He0Yu Liu1Mano R. Maurya2Paula Benny3Cameron Lassiter4Hui Li5Shankar Subramaniam6Lana X. Garmire7Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USADepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USADepartment of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USAUniversity of Hawaii Cancer Center, Department of Epidemiology, Honolulu, HI, USAUniversity of Hawaii Cancer Center, Department of Epidemiology, Honolulu, HI, USADepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USADepartment of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USA; Departments of Computer Science & Engineering and Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA, USADepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; For correspondence: Lana X. GarmirePreeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. However, it is not well understood what lipids are involved in the development of this condition, and even less is known how these lipids mediate its formation. To reveal the relationship between lipids and preeclampsia, we conducted lipidomic profiling of maternal sera of 44 severe preeclamptic and 20 healthy pregnant women from a multiethnic cohort in Hawaii. Correlation network analysis showed that oxidized phospholipids have increased intercorrelations and connections in preeclampsia, whereas other lipids, including triacylglycerols, have reduced network correlations and connections. A total of 10 lipid species demonstrate significant changes uniquely associated with preeclampsia but not any other clinical confounders. These species are from the lipid classes of lysophosphatidylcholines, phosphatidylcholines (PCs), cholesteryl esters, phosphatidylethanolamines, lysophosphatidylethanolamines, and ceramides. A random forest classifier built on these lipids shows highly accurate and specific prediction (F1 statistic = 0.94; balanced accuracy = 0.88) of severe preeclampsia, demonstrating their potential as biomarkers for this condition. These lipid species are enriched in dysregulated biological pathways, including insulin signaling, immune response, and phospholipid metabolism. Moreover, causality inference shows that various PCs and lysophosphatidylcholines mediate severe preeclampsia through PC 35:1e. Our results suggest that the lipidome may play a role in the pathogenesis and serve as biomarkers of severe preeclampsia.http://www.sciencedirect.com/science/article/pii/S0022227521001000preeclampsialipidomicsmetabolomicspathwaybiomarkerhypertension |
| spellingShingle | Bing He Yu Liu Mano R. Maurya Paula Benny Cameron Lassiter Hui Li Shankar Subramaniam Lana X. Garmire The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia Journal of Lipid Research preeclampsia lipidomics metabolomics pathway biomarker hypertension |
| title | The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| title_full | The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| title_fullStr | The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| title_full_unstemmed | The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| title_short | The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| title_sort | maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia |
| topic | preeclampsia lipidomics metabolomics pathway biomarker hypertension |
| url | http://www.sciencedirect.com/science/article/pii/S0022227521001000 |
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