Systemic and Placental α-Klotho: Effects of Preeclampsia in the Last Trimester of Gestation

• Published in: Placenta (Eastbourne) 2016-05, Vol.41, p.53-61
• Main Authors: Loichinger, Matthew H, Towner, Dena, Thompson, Karen S, Ahn, Hyeong J, Bryant-Greenwood, Gillian D
• Format: Article
• Language: English
• Subjects: Accelerated villous maturation; ADAM17 Protein - analysis; Adult; Extraembryonic Membranes - chemistry; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors - metabolism; Gestational Age; Glucuronidase - analysis; Glucuronidase - blood; Humans; Hypertension; Internal Medicine; Klotho; Klotho Proteins; Obstetrics and Gynecology; Placenta - chemistry; Pre-Eclampsia - physiopathology; Preeclampsia; Pregnancy; Pregnancy Trimester, Third; Receptors, Fibroblast Growth Factor - analysis; Trophoblasts - chemistry
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2016.03.004

Abstract Introduction 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. Methods Maternal blood, placenta and fetal membranes from 61 women (31 with PE and 30 controls) between 32-40 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. Results 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 32-40 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. Discussion 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.