Investigating the effects of oleic acid in the human placenta on inflammation, oxidative stress, and endothelial dysfunction associated with preeclampsia — ASN Events
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  3. Investigating the effects of oleic acid in the human placenta on inflammation, oxidative stress, and endothelial dysfunction associated with preeclampsia

Investigating the effects of oleic acid in the human placenta on inflammation, oxidative stress, and endothelial dysfunction associated with preeclampsia (#507)

Leia M Casci 1 , Louise C Rowntree 2 , Katherine Kedzierska 2 , Natasha de Alwis 1 , Natalie J Hannan 1
  1. Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Background 

Placental dysfunction is central to preeclampsia. Previously, we identified that OLAH, the enzyme responsible for oleic acid (OA) synthesis, is elevated in placentas from cases of preterm preeclampsia. Our team also found that OA drives immune perturbations in severe viral respiratory infection. Here we aimed to examine the role of OA in the human placenta and its effect on key pathways involved in placental function. 

Methods 

Term placental explant tissue (n=5), isolated primary human umbilical vein endothelial cells (HUVECs; n=5), and cytotrophoblasts (n=5) were treated with OA (100-750µM; physiological and pathological concentrations) for 24 hours. HUVECs and cytotrophoblasts were cultured in tumor necrosis factor (TNF) or hypoxia (1% oxygen) respectively to model dysfunction. Expression of inflammatory, oxidative stress, and endothelial dysfunction markers were assessed by qPCR.  

Results 

In placental explants, 750µM OA downregulated inflammatory IL-6 and COX2, but did not alter TNF expression. Likewise, 750µM OA decreased expression of antioxidant molecules (HO1, NQO1, TXN, GCLC)., but increased expression of oxidative stress marker NOX4. 

Similarly, 500-750µM OA reduced IL-6 and COX2 expression in cytotrophoblasts, in addition to TNF, growth factors PGF and IGF2, antioxidant molecules and NOX4, under both standard and hypoxic conditions. 

In HUVECs, 750µM OA downregulated inflammatory markers (IL-6, COX2, CCL2), adhesion molecules (ICAM1, VCAM1), and vasoconstrictor EDN1, while upregulating NOS3, a vasodilation mediator, under normal and dysfunctional conditions. Increased HO1 expression was observed with 500-750µM OA treatment in HUVECs under both conditions, and reduced NOX4 and GCLC expression under dysfunctional conditions. 

Conclusion 

These findings suggest that OA plays roles in placental inflammation and oxidative stress through cell-specific regulation in these pathways. Moreover, our findings suggest that OA may have a protective role in the endothelium and vasculature. Future studies evaluating soluble mediators and vasoreactivity will further uncover OA’s role in placental dysfunction associated with preeclampsia.