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Atheroprotective Actions of Oxytocin in Human Macrophages: Reduced Lipid Accumulation under Inflammatory Conditions

Ariel Karten1, Lora J. Kasselman2, Heather A. Renna2, Eric Lam3, Daniel S. Glass2, Nicholas A. Vernice2, Joshua DeLeon2, Allison B. Reiss2. 1Montefiore, Flushing, New York, United States, 2NYU Winthrop, Mineola, New York, United States, 3NYCOM at NYIT, Glen Head, New York, United States

Purpose of Study Oxytocin (OT) is a neuropeptide hormone secreted by the posterior pituitary gland physiologically associated with parturition, lactation, and other reproductive functions, and psychologically associated with affiliative behavior and anxiolytic effects. Deficits in OT action have been observed in patients with a variety of behavioral and mood disorders, and OT plasma levels correlate with increased cardiovascular disease (CVD) risk in such patients. Recent research reveals a wider systemic role for OT in modulation of inflammatory processes and development of atherosclerotic plaque. This study investigated the effects of OT on cholesterol transport and lipid uptake in THP-1 human macrophages, a pertinent model of atherosclerosis.
Methods Used THP-1 differentiated macrophages were untreated or treated with the pro-inflammatory activator lipopolysaccharide (LPS), 100 pM OT, or 1,10,100, 1000 pM OT + 100 ng LPS for 18-24 hours. Intracellular RNA was isolated using Trizol reagent and changes in cholesterol transporter gene expression levels were analyzed by real time quantitative PCR (RT-qPCR). Changes in protein expression were evaluated on extracts from whole cell lysates by Western blot. Oxidized LDL uptake and cellular cholesterol efflux capacity were measured with a quantitative fluorimetric assay.

Summary of Results In THP-1 macrophages, RT-qPCR revealed a significant increase in mRNA for the atheroprotective cholesterol export protein ATP binding cassette transporter (ABC)G1 upon OT treatment compared to LPS alone (p=0.0081), with Western blot confirming increased ABCG1 protein. Oxidized LDL uptake showed a significantly lower fluorescent value in OT-treated cells versus LPS alone (p<0.0001). While not statistically significant, (p=0.06), cholesterol efflux capacity increased with OT.
Conclusions OT is an endogenous peptide that can mitigate pro-atherogenic effects of the inflammatory environment incited by LPS exposure in THP-1 human macrophages. These findings support the hypothesis that OT has the potential to reduce pro-atherogenic arterial lipid accumulation in patients with heightened CVD risk, an effect that may be amplified in persons with low plasma OT.

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