INTRODUCTION: Preeclampsia (PE) affects between 3-8% of all pregnancies worldwide. Currently with no effective treatment, it is a leading cause of maternal and fetal death, particularly in the developing world. Elevated tumour necrosis factor (TNFα) reported in preeclamptic patients is thought to contribute to systemic endothelial dysfunction, which is a characteristic of PE. The peptide hormone relaxin has been attributed to many biological and haemodynamic effects in pregnancy and also considered as a possible treatment for vascular diseases. The aim of this study was to investigate whether or not relaxin peptides can reverse endothelial dysfunction induced by TNFα in vitro.
METHODS: Primary human umbilical vein endothelial cells (HUVECs) were isolated from healthy term placentas and treated with TNFα (0, 10, 1,000 and 10,000 pg/ml) with and without recombinant human relaxin (rhRLX: 1, 10 and 100 nM) or a relaxin peptide mimetic (B7-33: 10 nM) for 24h in a 5% CO2 humidified atmosphere at 37oC (). Following treatment endothelin-1 (ET-1), NADPH oxidase 2 (NOX2) and endothelial nitric oxide synthase (eNOS) mRNA expression was examined by qRT-PCR as markers of endothelial dysfunction.
RESULTS: TNFα treatment resulted in dose-dependent increase in ET-1 and NOX2 mRNA expression but had no effect on eNOS. In the presence of rhRLX, there was a significant (p<0.05, One-way ANOVA) reduction in NOX2 expression but no effect on ET-1 and eNOS. Similarly, 10nM B7-33 caused a reduction in NOX2 but this mimetic failed to reach significance (p=0.052). This suggests that B7-33 is not as potent as rhRLX in HUVECs.
CONCLUSION: This study demonstrated that relaxin peptides reduce NOX2 and endothelial dysfunction in HUVECs. The likely mechanism involves a relaxin-induced decrease in oxidative stress (NADPH oxidase activity).
rhRLX was provided by Novartis Pharma AG; B7-33 was provided by Dr. Akhter Hossain (Howard Florey Institute)