Eicosapentaenoic acid inhibits ICAM-1 expression in pulmonary endothelial cells with inflammation

ABSTRACT

INTRODUCTION: Infectious agents like SARS-CoV-2 trigger inflammation in endothelial cells (EC) in multiple vascular beds in infected patients, including pulmonary tissue that leads to acute respiratory distress syndrome (ARDS). Due to its anti-inflammatory effects, the omega-3 fatty acid eicosapentaenoic acid (EPA) is being tested in patients at risk for COVID-19. Additionally, EPA has been shown to significantly reduce cardiovascular events in high risk patients with elevated triglycerides as reported in the REDUCE-IT trial. The objective, then, of this study was to test the ability of EPA to reduce inflammatory changes in pulmonary ECs. 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 lipopolysaccharide (LPS) at 200 ng/mL for 24 h. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in pulmonary ECs was measured with immunochemistry using SDS-PAGE and compared with β- Actin as a control. RESULTS: HMVEC-L challenged with LPS dramatically increased ICAM-1 expression by 1135% (p<0.001) compared with vehicle treatment. Pulmonary ECs pretreated with EPA had reduced expression of ICAM-1 by 47% (p<0.001). LPS modestly increased VCAM-1 expression (45%, p<0.05) in a manner that was reduced by EPA (12%), but it was not significant. CONCLUSIONS: EPA significantly reduced the expression of ICAM-1 in human pulmonary ECs following LPS exposure. These studies indicate a protective effect of EPA on the pulmonary endothelium that may reduce inflammation associated with infectious agents such as SARS-CoV-2.