title: Systemic and placental α-klotho: Effects of preeclampsia in the last trimester of gestation.
abstract: α-klotho is an anti-aging protein, potentially important in preeclampsia (PE). Produced by kidney, brain and placenta, and by mRNA splicing is both a full-length membrane-bound and a truncated soluble protein in the circulation. The membrane-bound protein is an obligate co-receptor for fibroblast growth factor 23 (FGF23) and its action on receptor (FGFR), but ADAM proteinases also cause its shedding. The aims of this study were to investigate levels of maternal plasma, placental, and fetal membrane α-Klotho and their association with placental accelerated villous maturation (AVM) in PE. In addition, placental and membrane levels of ADAM17 and FGFR were measured in the same patients.
  
  
  
  Maternal blood, placenta and fetal membranes from 61 women (31 with PE and 30 controls) between 32 and 40 weeks gestation were collected. Plasma α-klotho was measured by ELISA, and quantitative immunohistochemistry used for α-klotho, ADAM17 and FGFR1 in tissues. Placental AVM was histologically assessed.
  
  
  
  Maternal plasma levels of α-Klotho were higher in PE compared to controls (p = 0.01) and patients with the highest levels had significantly less AVM (p = 0.03). α-Klotho, ADAM17, and FGFR were all present in syncytiotrophoblast and cytotrophoblast of membranes. Between 32 and 40 weeks gestation, all placental levels decreased in controls respectively (p = 0.04, p = 0.004, p = 0.05), but not in PE. Fetal membrane levels were unchanged.
  
  
  
  Maternal plasma α-Klotho was increased in PE and its levels associated with reduced placental AVM. Changes in placental α-Klotho, ADAM17, and FGFR suggest their involvement in the pathophysiology of PE.
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, 1319 Punahou Street, Suite 824, Honolulu, HI 96826, USA. Electronic address: mloichin@gmail.com.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Loichinger
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, 1319 Punahou Street, Suite 824, Honolulu, HI 96826, USA. Electronic address: dtowner@hawaii.edu.
authors.forename: Dena
authors.initials: D
authors.lastname: Towner
authors.affiliation: Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: karenst@hawaii.edu.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Thompson
authors.affiliation: Biostatistics Core, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: hjahn@hawaii.edu.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, 1319 Punahou Street, Suite 824, Honolulu, HI 96826, USA. Electronic address: gbg@pbrc.hawaii.edu.
authors.forename: Gillian D
authors.initials: GD
authors.lastname: Bryant-Greenwood
mesh_terms: D000072198:ADAM17 Protein / Q000032:analysis; D000328:Adult; D005321:Extraembryonic Membranes / Q000737:chemistry; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005865:Gestational Age; D005966:Glucuronidase / Q000032:analysis* / Q000097:blood; D006801:Humans; D000090265:Klotho Proteins; D010920:Placenta / Q000737:chemistry*; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis; D014327:Trophoblasts / Q000737:chemistry
chemical_list: C000717427:FGF23 protein, human; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: Accelerated villous maturation; Hypertension; Klotho; Preeclampsia; Pregnancy