Total Versus Free Placental Growth Factor Levels in the Pathogenesis of Preeclampsia
| Autor: | Saira Salahuddin, Ambart E. Covarrubias, S. Ananth Karumanchi, Agnes Lo, Edouard Lecarpentier, Zsuzsanna K. Zsengellér, Bassam Haddad, Ravi Thadhani |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Placental growth factor medicine.medical_specialty Placenta Neovascularization Physiologic 030204 cardiovascular system & hematology Preeclampsia Pathogenesis 03 medical and health sciences 0302 clinical medicine Pre-Eclampsia Pregnancy Internal medicine Internal Medicine medicine Humans Placenta Growth Factor Immunoassay Vascular Endothelial Growth Factor Receptor-1 030219 obstetrics & reproductive medicine Proteinuria Chemistry medicine.disease Immunohistochemistry Real-time polymerase chain reaction Endocrinology medicine.anatomical_structure embryonic structures Female medicine.symptom Biomarkers Ex vivo |
| Zdroj: | Hypertension. 76:875-883 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.120.15338 |
| Popis: | Elevated circulating sFLT-1 (soluble fms-like tyrosine kinase) and low levels of its ligand, PlGF (placental growth factor), are key characteristics of preeclampsia. However, it is unclear if the low levels of plasma PlGF noted during preeclampsia are due to decreased placental production of PlGF or due to binding of PlGF by increased circulating sFLT-1. Here, we describe a biochemical procedure to dissociate PlGF-sFLT-1 complex ex vivo and when used in conjunction with an immunoassay platform, demonstrate a method to measure total and free PlGF in human blood samples. Using this method, we noted that plasma free PlGF levels were significantly lower in preeclampsia (N=22) than in nonhypertensive controls (N=24; mean, 314 versus 686 pg/mL, P P =0.49). In contrast, total sFLT-1 levels were significantly higher in preeclampsia than in nonhypertensive controls (mean, 16 957 versus 3029 pg/mL, P r 2 =0.68). We confirmed these findings in an independent cohort of subjects (N=49). Furthermore, we did not detect any difference in PlGF mRNA by quantitative polymerase chain reaction or in PlGF protein expression by immunohistochemistry in preeclamptic placentas when compared with nonhypertensive controls. In contrast, sFLT-1 mRNA and protein levels were upregulated in placentas from women with preeclampsia. Taken together with prior studies, our results provide evidence that decrease in circulating PlGF noted during preeclampsia is largely mediated by excess circulating sFLT-1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|