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(Hypertension. 2009;54:106.)
© 2009 American Heart Association, Inc.

Original Articles

Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia and in Pregnancy Complicated by Diabetes Mellitus

Meryam Sugulle; Ralf Dechend; Florian Herse; M. Susanne Weedon-Fekjaer; Guro M. Johnsen; K. Bridget Brosnihan; Lauren Anton; Friedrich C. Luft; Kai C. Wollert; Tibor Kempf; Anne Cathrine Staff

From the Department of Obstetrics and Gynaecology (M.S., A.C.S.), Oslo University Hospital, Ulleval, Norway; Faculty of Medicine (M.S., A.C.S.) and Department of Nutrition (M.S.W.-F., G.M.J.), University of Oslo, Oslo, Norway; Medical Faculty of the Charité (R.D., F.H., F.C.L), Franz-Volhard Clinic, HELIOS Klinikum Berlin, Berlin, Germany; Hypertension and Vascular Research Center (K.B.B., L.A.), Wake Forest University School of Medicine, Winston-Salem, NC; and the Department of Cardiology and Angiology (K.C.W., T.K.), Hannover Medical School, Hannover, Germany.

Correspondence to Anne Cathrine Staff, Department of Obstetrics and Gynaecology, Oslo University Hospital, Ulleval, Kirkeveien 166, 0450 Oslo, Norway. E-mail annetine.staff{at}ulleval.no

Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-β–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.

Key Words: cardiovascular disease • growth differentiation factor 15 • preeclampsia • diabetes mellitus • pregnancy