Race-Dependent Modulation of Endothelial Cell Responses to Shear Stress: Implications for Vascular Health in African Americans

Abstract

It is known that African American ethnicity is an independent risk factor for exaggerated oxidative stress which is intricately intertwined with inflammation, hypertension (HT), and cardiovascular disease (CVD). The purpose of this dissertation study was to examine the racial differences that exist between African Americans and Caucasians in oxidative stress levels at the molecular level using an in vitro model of Human Umbilical Vein Endothelial Cells (HUVECs). African American HUVECs were found to have significantly higher baseline levels of oxidative stress in vitro compared to Caucasian HUVECs. In order to establish proof of concept, three preliminary studies were conducted. The first preliminary study, an acute exercise protocol was conducted in young healthy adults in order to measure plasma oxidative stress markers in response to a single moderate intensity treadmill exercise bout. In this study, it was found that the treadmill exercise did not elicit a race-dependent responses, but that African American adults had higher level of oxidative stress at all sample times when compared to the Caucasians. A second preliminary study was conducted using a parallel cell culture design to measure basal oxidative stress levels in African American and Caucasian HUVECs without stimulation. These data were shown in relation to the plasma levels of oxidative stress in resting African American and Caucasian adults. This was done in order to show that the common oxidative stress markers measured in human plasma can also be measured in cell culture supernatant and lysate. It was found that both African American adults and HUVECs had heightened oxidative stress and inflammatory markers when compared to their Caucasian counterparts. The third preliminary study was conducted using tumor Necrosis Factor-#945; (TNF-#945;) as an inflammatory stimulant and measuring the oxidative stress response in both African American and Caucasian HUVECs. This was done in order to show that cells of different race respond differently to stimuli. It was found that the response to TNF-α was blunted in African American HUVECs. The final step was to use laminar shear stress (LSS) as an exercise mimetic in order to examine whether HUVECs from different race respond differently. HUVECs from both race were harvested under static condition (no LSS), with low LSS at 5 dyne/cm2, and with a moderate level of LSS at 20 dyne/cm2. It was found that despite the fact that African American HUVECs had higher levels of oxidative stress under static conditions, when LSS was applied, protein expressions and oxidative stress biomarkers adjusted to levels that were similar to the Caucasian HUVEC adaptations to LSS. From this, it appears that African American HUVECs have a larger response to LSS stimulus indicating that aerobic exercise prescriptions may be valuable for this population since the potential exists for large improvements in oxidative stress levels for this population.