Abstract 037: Serum Chemerin As A Novel Biomarker For Preeclampsia Complications: Effects Of Statins On Its Release From The Placenta

Background: The adipokine chemerin is increased in preeclampsia (PE), possibly because it is released from the placenta. We aimed to evaluate the potential of chemerin as novel biomarker to predict PE or PE-related complications. Methods: Making use of a secondary analysis of a prospective cohort study that evaluated the usefulness of the sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor), we measured chemerin in 371 women with suspected or confirmed PE. In addition, we obtained placentas from 25 women (15 healthy controls, 10 PE) to determine whether statins are capable of reducing chemerin release from isolated perfused placentas and placental explants. For this purpose, chemerin, sFlt-1 and PlGF were measured in the perfusate before and after the addition of 1000 ng/mL pravastatin or 6000 ng/mL fluvastatin to the maternal side, and in explant cultured medium before and after exposure to pravastatin (10, 100 or 1000 μmol/L) or fluvastatin (10 or 100 μmol/L) for 72 hours at 37°C with 5% O 2 and 5% CO 2 . Results: At time of biomarker measurement, women had a median gestational age of 35.6 weeks (range 31.7-38.0). Serum chemerin levels were elevated (P<0.001) in women with confirmed PE (n=85) and gestational hypertension (n=68) in comparison to those without hypertensive disease of pregnancy (n=218; 243±13 and 205±19 vs. 185±6 ng/mL). Serum chemerin correlated positively with the sFlt-1/PlGF ratio (r=0.27, P<0.001), the protein/creatinine ratio (r=0.27, P<0.001), and mean arterial blood pressure (r=0.20, P<0.001), and negatively with birth weight (r=-0.24, P<0.001). Levels of chemerin were significantly higher in maternal perfusate of preeclamptic placentas in comparison to healthy placentas. Pravastatin, but not fluvastatin, suppressed chemerin and sFlt-1 release from healthy placentas, and upregulated PlGF release. Studies in placental explants confirmed this observation. Conclusions: Chemerin is increased in both serum and placental perfusate of women with PE, and should therefore be investigated as a potential biomarker for PE or PE-related complications. Moreover, pravastatin lowered placental chemerin release in parallel with sFlt-1, suggesting that the 2 might be causally linked.