Protective proteins and telomere length in placentas from patients with pre-eclampsia in the last trimester of gestation.
Visfatin/nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in energy metabolism and sirtuins, SIRT1 and SIRT3, which are NAD-dependent deacetylases, are critical for cellular function. All three either regulate or are regulated by intracellular NAD+ levels and therefore available cellular energy, important for placental cell survival and successful pregnancy. This study investigates whether these protective proteins are involved in the placental pathophysiology of pre-eclampsia (PE) and if they are associated with 8-oxo-deoxyguanosine (8OHdG), a marker of oxidative damage or with placental telomere length.



Maternal blood and placental samples were collected from 31 patients with PE and 30 controls between 31 and 40 weeks gestation. Quantitative immunohistochemistry was performed on placental specimens for visfatin/Nampt, SIRT1, SIRT3, and nuclear 8OHdG. Plasma visfatin was measured by ELISA and telomere length by Southern blot analysis of telomere restriction fragments.



Visfatin/Nampt and SIRT1 in syncytiotrophoblast decreased in PE compared to controls (p < 0.0001, p = 0.004 respectively). SIRT3 decreased in PE most significantly at preterm (p = 0.002). 8OHdG was only significantly lower in preterm controls compared to term controls (p = 0.01) and correlated with SIRT1 in all samples (r = 0.27). Telomere length was not different in PE and controls.



Decreased visfatin/Nampt, SIRT1 and SIRT3 in syncytiotrophoblast in PE suggests a lack of placental reserve in metabolic energy efficiency, increased inflammation, and lower resistance to environmental stressors. However, there was little effect on nuclear function, or evidence of genomic DNA damage, which would lead to cellular senescence and death.
Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: abroady@hawaii.edu.
Autumn J
AJ
Broady
Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: Matthew.Loichinger@allina.com.
Matthew H
MH
Loichinger
Office of Biostatistics and Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: hjahn@hawaii.edu.
Hyeong Jun
HJ
Ahn
Department of Anatomy and Reproductive Biology, Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: pdavy@hawaii.edu.
Philip M C
PM
Davy
Department of Anatomy and Reproductive Biology, Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: allsopp@hawaii.edu.
Richard C
RC
Allsopp
Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: gbg@pbrc.hawaii.edu.
Gillian D
GD
Bryant-Greenwood
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D056564:Sirtuin 1 / Q000378:metabolism*; D056566:Sirtuin 3 / Q000378:metabolism*; D016615:Telomere; D014327:Trophoblasts / Q000378:metabolism
D015415:Biomarkers; D054409:Nicotinamide Phosphoribosyltransferase; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3
8-Oxo-deoxyguanosine; Hypertension; Pre-eclampsia; Sirtuins; Telomeres; Visfatin