Year: 2018
Type: article
Abstract: Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1. Notably, PlGF KO mice had morphologically distinct placentas, showing an accumulation of junctional zone glycogen. We next considered the role of placental PlGF in an established model of preeclampsia (pregnant catechol-O-methyltransferase-deficient [COMT-deficient] mice) by generating mice with deletions in both the Pgf and Comt genes. Deletion of placental PlGF in the context of COMT loss resulted in a reduction in maternal blood pressure and increased placental glycogen, indicating that loss of PlGF might be protective against the development of preeclampsia. These results identify a role for PlGF in placental development and support a complex model for the pathogenesis of preeclampsia beyond an angiogenic factor imbalance.
DOI: 10.1172/jci99026
Institutions: The University of Texas MD Anderson Cancer Center, Baylor College of Medicine, The University of Texas Health Science Center at Houston, Beth Israel Deaconess Medical Center, Harvard University, Indiana University Indianapolis, Indiana University School of Medicine, University of Pennsylvania, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Mayo Clinic, Brigham and Women's Hospital, Vlaams Instituut voor Biotechnologie, VIB-KU Leuven Center for Cancer Biology, KU Leuven
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Role of Fibroblasts, Myeloid Cells and Matrix in PDAC, Targeting Pericytes in Cancer, Regulation of Angiogenesis by Tumstatin, Epigenetic Modifications in Renal Fibrogenesis, Exosomes in Cancer Therapy, Stromal Regulation of Bone Metastasis, Employing mouse models to translate early detection of pancreas cancer, Assembly of Type IV Collagen in Health and Disease, Genetics and Biology of Pancreatic Ductal Adenocarcinoma
OpenAlex ID: W2891553188