Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

International Journal of Molecular Sciences

Birgit Hirschmugl¹  Silvija Cvitic¹  Violeta Simovic¹  WaltraudT. Brandl¹  Jasmin Strutz¹  Elisa Weiß¹  Ursula Hiden¹  HannahM. Berger¹  Carmen Tam-Ammersdorfer² 

[1] Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria;Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, 8036 Graz, Austria;

关键词: mme;    neprilysin;    maternal overweight;    feto-placental endothelial cells;    umbilical cord blood;   

DOI  :  10.3390/ijms21030834

来源: DOAJ

【 摘 要 】

Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.

【 授权许可】

Unknown