Eicosapentaenoic acid preserves pulmonary endothelial nitric oxide release following lps challenge

ABSTRACT

INTRODUCTION: Endothelial cell (EC) dysfunction results in reduced nitric oxide (NO) bioavailability leading to inflammation and thrombus formation. Infectious agents like SARS-CoV-2 and influenza can infect ECs in multiple vascular beds from different organs in infected patients, especially in the lung. The omega-3 fatty acid eicosapentaenoic acid (EPA) and its metabolites can preserve EC function and reduce inflammation. These effects of EPA likely contribute to reduced cardiovascular events as reported in REDUCE-IT. Currently, EPA is being tested in patients at risk for COVID-19. This study tested the effects of EPA on NO bioavailability in pulmonary ECs under conditions of inflammation induced by lipopolysaccharide (LPS). METHODS: Human lung microvascular endothelial cells (HMVEC-L) were pretreated with vehicle or EPA (40 μM) in 2% FBS for 2 h, then challenged with LPS at 200 ng/ml for 24 h. Cells (including untreated controls) were stimulated with calcium ionophore to measure maximum production of NO and peroxynitrite (ONOO-) using tandem porphyrinic nanosensors. RESULTS: HMVEC-L challenged with LPS showed a pronounced loss of NO bioavailability. Cells treated with EPA increased NO release (20%, p<0.05) and decreased ONOO- release (14%, p<0.01) compared with LPS treatment. The [NO]/[ONOO-] ratio, a marker of eNOS coupling efficiency, decreased by 39% (p<0.001) following exposure to LPS. However, EPA increased the ratio by 39% (p<0.01) compared with LPS alone. CONCLUSIONS: These findings indicate that EPA preserves NO bioavailability and reduces nitroxidative stress in pulmonary ECs following LPS treatment. These studies indicate a protective effect of EPA on pulmonary ECs that may reduce the inflammatory changes caused by infectious agents such as influenza or SARS-CoV-2 among other stimuli.