Racial Disparity in Cardiovascular Disease and Oxidative Stress in African American Women

Abstract

ABSTRACT Several studies have demonstrated that African Americans (AA) exhibit elevations in systemic oxidative stress compared to Caucasian Americans (CA). Peripheral blood mononuclear cells (PBMCs) have been identified as one of the primary contributors to systemic reactive oxygen species (i.e. oxidative stress) via the NADPH enzyme pathway and may be an underlying mechanism for the development of hypertension and cardiovascular diseases. Previous work demonstrates that young healthy AA men have elevated PBMC-derived superoxide production when compared to CA men. However, whether PBMC-derived superoxide production is also elevated in young healthy AA women remains unknown. Accordingly, this study investigated PBMC-derived superoxide production in young healthy AA and CA women. We tested the hypothesis that, relative to CA women, AA women would exhibit greater PBMC-derived intracellular superoxide with corresponding expressions of the NADPH oxidase subunit proteins. Superoxide of intracellular superoxide. In ten normotensive AA women and twelve age-matched normotensive CA women, resting intracellular superoxide levels were assessed from freshly isolated PBMCs using dihydroethidium fluorescence within one hour of venous blood sampling. PBMCs were frozen in -80ºC and protein was later extracted to assess expression of the NADPH-oxidase subunits p47phox (cytosolic) and gp91phox (membranous) using Western blot analysis in a subset of subjects (AA n=7, CA= n=5). Significantly higher resting intracellular superoxide production was found in AA women compared to CA (AA 4.1±1.9 vs. CA 2.7±1.0 Relative Fluorescent Units; P=0.025) as well as elevated protein expression of p47phox (e.g., p47phox: 3.7 ± 1.5, AA vs. 0.5 ± 0.2, CA, P < 0.05). Interestingly, there was no found difference in gp91phox expression among the AA and CA women (gp91phox 5.4 ± 2.4, AA vs. 4.4 ± 0.8, CA women, P < 0.05). These findings indicate that young AA women exhibit greater resting PBMC-derived superoxide production and suggest the NADPH-oxidase pathway may play a role in their elevation in superoxide production. Thus, PBMCs may represent a source of elevated oxidative stress in AA women.