title: Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms.
abstract: Preeclampsia (PE) is a pregnancy-specific disorder typically presenting as new-onset hypertension and proteinuria. While numerous epidemiological studies have demonstrated that obesity increases the risk of PE, the mechanisms have yet to be fully elucidated. Growing evidence from animal and human studies implicate placental ischemia in the etiology of this maternal syndrome. It is thought that placental ischemia is brought about by dysfunctional cytotrophoblast migration and invasion into the uterus and subsequent lack of spiral arteriole widening and placental perfusion. Placental ischemia/hypoxia stimulates the release of soluble placental factors into the maternal circulation where they cause endothelial dysfunction, particularly in the kidney, to elicit the clinical manifestations of PE. The most recognized of these factors are the anti-angiogenic sFlt-1 and pro-inflammatory TNF-α and AT1-AA, which promote endothelial dysfunction by reducing levels of the provasodilator nitric oxide and stimulating production of the potent vasoconstrictor endothelin-1 and reactive oxygen species. We hypothesize that obesity-related metabolic factors increase the risk for developing PE by impacting various stages in the pathogenesis of PE, namely, 1) cytotrophoblast migration and placental ischemia; 2) release of soluble placental factors into the maternal circulation; and 3) maternal endothelial and vascular dysfunction. This review will summarize the current experimental evidence supporting the concept that obesity and metabolic factors like lipids, insulin, glucose, and leptin affect placental function and increase the risk for developing hypertension in pregnancy by reducing placental perfusion; enhancing placental release of soluble factors; and by increasing the sensitivity of the maternal vasculature to placental ischemia-induced soluble factors.
authors.affiliation: Department of Physiology and Biophysics, Cardiovascular-Renal Research Center, Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Spradley
authors.affiliation: Department of Physiology and Biophysics, Cardiovascular-Renal Research Center, Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Palei
authors.affiliation: Department of Physiology and Biophysics, Cardiovascular-Renal Research Center, Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi jgranger@umc.edu.
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D054392:Adipokines / Q000378:metabolism; D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007511:Ischemia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D021041:Placental Circulation; D011225:Pre-Eclampsia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D042501:Angiogenic Proteins; D018836:Inflammation Mediators
keywords: RUPP; body mass index; inflammation; placental ischemia; pregnancy; sFlt-1