Racial differences in tumor necrosis factor-α-induced endothelial microparticles and interleukin-6 production
Michael D Brown1,3, Deborah L Feairheller1, Sunny Thakkar1, Praveen Veerabhadrappa1, Joon-Young Park2
1Hypertension, Molecular and Applied Physiology Laboratory, 2Cardiovascular Genomics Laboratory, Department of Kinesiology, 3Cardiovascular Research Center, School of Medicine, Temple University, Philadelphia, PA, USA
Abstract: African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF- α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/µg in the AA and 30.9 ± 14.9 pg/mL/µg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α.
Keywords: endothelium, inflammation, endothelial microparticles, African Americans
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