Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia
In a cohort of early postpartum individuals, we observed greater <i>METAP1</i> expression in venous ECs of women with preeclampsia versus normotensive delivery. Mendelian randomization supported a causal relationship between greater vascular <i>METAP1</i> expression and higher preeclampsia risk, and functional experiments demonstrated antiangiogenic and proinflammatory effects of METAP1 in human ECs consistent with alterations observed in preeclampsia. Ex vivo EC transcriptomics can identify novel mechanisms underlying preeclampsia pathophysiology, with implications for prevention and treatment.
Authors
- Jennifer E. Ho (ORCID: https://orcid.org/0000-0002-7987-4768)
- Maria A. Pabón (ORCID: https://orcid.org/0000-0003-1883-0654)
- Ruslan I. Sadreyev (ORCID: https://orcid.org/0000-0002-4240-5466)
- Michael C. Honigberg (ORCID: https://orcid.org/0000-0001-8630-5021)
- Naomi M. Hamburg (ORCID: https://orcid.org/0000-0001-5504-5589)
- Peng Xia (ORCID: https://orcid.org/0000-0002-3422-6695)
- Emily S. Lau (ORCID: https://orcid.org/0000-0001-9361-6397)
- Yanxi Shi
- Claire Castro (ORCID: https://orcid.org/0000-0002-6309-1689)
- Jiayi Kang (ORCID: https://orcid.org/0000-0001-7784-6432)
- Maddalena Ardissino (ORCID: https://orcid.org/0000-0002-2654-8117)
- Anna Perillo (ORCID: https://orcid.org/0009-0009-0083-2759)
- Katherine E. Economy (ORCID: https://orcid.org/0000-0001-6359-0739)
- Robert M. Weisbrod (ORCID: https://orcid.org/0000-0002-8297-2975)
- Antonio de Marvao (ORCID: https://orcid.org/0000-0001-9095-5887)
- Nandita S. Scott (ORCID: https://orcid.org/0000-0003-3261-7833)
- Sanjay Divakaran (ORCID: https://orcid.org/0000-0003-0598-6502)
- Leanne Barrett (ORCID: https://orcid.org/0000-0003-0667-8720)
- Jenifer M. Brown (ORCID: https://orcid.org/0000-0002-6647-639X)
- Jason D. Roh (ORCID: https://orcid.org/0000-0002-6999-6868)
- Murat Çetinbaş (ORCID: https://orcid.org/0000-0002-7516-8225)
- Marcelo F. Di Carli (ORCID: https://orcid.org/0000-0003-3119-025X)
- Haobo Li (ORCID: https://orcid.org/0000-0002-5660-7835)
- Zihui Yang (ORCID: https://orcid.org/0000-0003-1457-5107)
- Eunice Kim
- Malissa J. Wood (ORCID: https://orcid.org/0000-0003-0482-1116)
Institutions
- Broad Institute (US)
- Boston University (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- King's College London (GB)
- University of Cambridge (GB)
- General Medical Council (GB)
- Hammersmith Hospital (GB)
- Harvard University Press (US)
- British Heart Foundation (GB)
- National Institute for Health and Care Research (GB)
- Massachusetts General Hospital (US)
- Lee Memorial Health System (US)
- MRC London Institute of Medical Sciences (GB)
- Medical Research Council (GB)
Publication Details
- Journal
- Circulation Research
- Published
- 2024-12-27
- DOI
- https://doi.org/10.1161/circresaha.124.324606
- Citations
- 2
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 1.17