Effects of Shear Stress on Oxidized LDL Modulation of miRNA Expression in African American and Caucasian Endothelial Cell Lines

Abstract

Endothelial dysfunction is a leading cause of atherosclerosis and cardiovascular disease (CVD). Oxidized LDL (oxLDL) and microRNAs (miRNAs) have been shown to play crucial roles in the development and progression of endothelial dysfunction. Interestingly, African Americans have a higher rate of developing endothelial dysfunction and CVD compared to Caucasians. oxLDL concentrations and miRNA expression may be contributing to these racial differences. Furthermore, high shear stress (HSS) or aerobic exercise has been shown to prevent the development of CVD, lower concentrations of oxLDL, and alter expression of miRNAs. HSS can mitigate racial differences in endothelial function. Thus, we conducted the present study to expound the potential racial divergences in five select miRNAs(miR-155, -4763-5p, -98, 106a-5p, and 142-3p) and seven proteins (VEGFA, eNOS, LC3, APOL3, Caspase-3, STAT-3, Rictor) that have been involved in oxLDL’s processes or endothelial cell health. Additionally, we investigated the beneficial role of exercise (or HSS) through these miRNAs and proteins. Human umbilical vein endothelial cells (HUVECs) from African American and Caucasian donors were used and subjected to oxLDL treatment and HSS. We reveal significant racial differences in miR-155, -4763-5p, and -98 expression, as well as, VEGFA, eNOS, LC3, APOL3, Caspase-3, STAT-3, and Rictor protein expression. We conclude that these miRNAs and proteins may be contributing to endothelial dysfunction disparities. Furthermore, HSS mimicking aerobic exercise plays a pivotal role in these differences.