NNMT expression in preeclampsia: Analyses on placental tissues and cell lines

Objective: Preeclampsia (PE) is a multisystem disorder characterized by new onset hypertension and proteinuria during pregnancy. Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA) and S-adenosyl-L-homocysteine (SAH). The aim of this study was to investigate NNMT expression in normal and PE placentas, and evaluate whether hypoxia, oxidative stress and inflammation could modulate NNMT expression. Materials and methods: Immunohistochemistry and Western blot were performed on first trimester, normal term and PE placentas. NNMT expression was also evaluated in HTR-8/SVneo and BeWo cell lines under hypoxic, oxidative stress (by H2O2) and inflammatory (by TNF-α) conditions. Results: NNMT was expressed in cytotrophoblast and syncytiotrophoblast of first, third and PE placentas. Endothelial vessels were positive for NNMT expression in first and third trimester but mainly negative in PE placentas. NNMT expression did not change from first to third trimester but significantly decreased in PE placentas compared to control placentas. NNMT was expressed in the cytoplasm of both HTR-8/SVneo and BeWo cell lines, and its expression was not altered by syncytialization. Hypoxia decreased NNMT expression in BeWo but not HTR-8/SVneo cells while oxidative stress did not alter NNMT expression in both cell lines. TNF-α treatment significantly decreased NNMT expression in both cell lines. Conclusions: Low NNMT expression found in PE placentas may represent a response to the hypoxia and inflammation featuring this disorder. Therefore, the enzyme could contribute to the normal human placental development, by defending trophoblast cells form PE-induced damages.