title: Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus.
abstract: Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-beta-related cytokine, is emerging as a new risk marker in patients with cardiovascular disease. We explored GDF-15 in preeclampsia and in diabetic pregnancies, because these conditions are associated with augmented risk for cardiovascular disease, both in mother and in offspring. Plasma from pregnant women (n=267; controls: n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental GDF-15 mRNA and protein expression levels were analyzed by quantitative real-time PCR and immunoblots in 78 and 18 pregnancies, respectively. Conditioned media from preeclamptic (n=6) and control (n=6) villous placenta explants were analyzed by immunoassay for GDF-15. Median maternal GDF-15 concentration was elevated in those with diabetes mellitus, as compared with controls (91 549 versus 79 875 ng/L; P=0.02). Median GDF-15 concentration was higher in patients with preeclampsia than in controls in term maternal blood samples (127 061 versus 80 319 ng/L; P<0.001). In the fetal circulation and amniotic fluid, GDF-15 was elevated in preeclampsia and superimposed preeclampsia in diabetes mellitus, as compared with controls. GDF-15 placental mRNA expression was elevated in preeclampsia, as compared with controls (P=0.002). Placenta immunoblots confirmed a single GDF-15 protein band, and a time-dependent increase in GDF-15 protein was detected in the conditioned media. Our study is the first to show that GDF-15 is dysregulated, both in preeclampsia and in diabetic pregnancies. The mechanisms and diagnostic implications of these findings remain to be explored.
authors.affiliation: Department of Obstetrics and Gynaecology, Oslo University Hospital, University of Oslo, Norway.
authors.forename: Meryam
authors.initials: M
authors.lastname: Sugulle
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.forename: M Susanne
authors.initials: MS
authors.lastname: Weedon-Fekjaer
authors.forename: Guro M
authors.initials: GM
authors.lastname: Johnsen
authors.forename: K Bridget
authors.initials: KB
authors.lastname: Brosnihan
authors.forename: Lauren
authors.initials: L
authors.lastname: Anton
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D007231:Infant, Newborn; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D046509:Tissue Culture Techniques; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger