Abstract 430: Race Dependent Effects of C Reactive Protein on the Vasomotor Modulators ET1 and NO in HUVECs

Background: Chronic inflammation and elevated levels of C reactive protein (CRP) can lead to reduced bioavailability of endothelium relaxing factors such as Nitric Oxide (NO) and increased production of vasoconstrictive pro-inflammatory agents such as endothelin-1 (ET1). African Americans (AA) have impaired vasodilatory capabilities evident through reduced NO bioavailability. The purpose of this study was to investigate the potential differential racial effect of CRP on ET1 and NO. METHODS: AA and Caucasian (C) Human Umbilical Vein Endothelial Cells (HUVECs) were cultured and treated with 0, 25, 50, and 100μg/mL CRP. The secretion of ET1 and NO in HUVEC culture medium supernatant was assessed by ELISA and a modified Griess assay, respectively. Results: At baseline (0μg/mL CRP) there were no significant differences between AA and C in ET1 (457.5 ± 44.8 vs 420.6 ± 34.8 pg/mL) or NO (8.0 ± 1.4 vs 7.4 ± 1.2 μmol/L). Differences (p≤.05) were found at 50μg/mL CRP between ET1 and NO between C and AA HUVECs (ET1: 566.7 ± 17.7 vs 595.8 ± 73.6 pg/mL) (NO: 0 ± 0 vs 1.1 ± 1.0 μmol/L). There was a significant increase in ET1 in the AA HUVECs from 0μg/mL (457.5 ± 44.8 pg/mL) to 25μg/mL CRP (546.8 ± 39.8 pg/mL) while NO decreased significantly in AA HUVECs from 0μg/mL (8.0 ± 1.4 μmol/L) to 25μg/mL (0.5 ± 0.2 μmol/L), 50μg/mL (1.1 ± 1.0 μmol/L), and 100μg/mL CRP (0.1 ± 0.1 μmol/L). C HUVECs showed significant changes in ET1 between 0μg/mL (420.6 ± 34.8 pg/mL) and 50μg/mL CRP (566.7 ± 17.7 pg/mL) and in NO from 0μg/mL CRP (7.4 ± 1.2 μmol/L) to 25μg/mL (0.8 ± 0.5 μmol/L), 50μg/mL (0 ± 0 μmol/L), and 100μg/mL (0.9 ± 0.6 μmol/L). Without the influence of race, significant increases in ET1 production occurred from 0μg/mL CRP (439.0 ± 39.8 pg/mL) to 25μg/mL (512.0 ± 38.9 pg/mL) (p ≤ 0.001) and 50μg/mL CRP (581.2 ± 45.6 pg/mL) and significant decreases in NO (p ≤ 0.001) from 0μg/mL CRP (7.7 ± 1.3 μmol/L) to 25μg/mL CRP (0.6 ± 0.4 μmol/L), 50μg/mL CRP (0.5 ± 0.5 μmol/L), and 100 μg/mL CRP (0.5 ± 0.3 μmol/L). Conclusions: Our data show that differential CRP induced ET1 and NO production does not appear to contribute to the difference in hypertension prevalence between AA and C. Further investigation is needed to determine the cause of the racial differences in Hypertension between African Americans and Caucasians.