Aerobic Exercise Training Effect on In Vivo and In Vitro Vascular Endothelial Inflammatory Indices in African Americans: Implications for Hypertension and Cardiovascular Health

Abstract

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to evaluate the in vivo influence of aerobic exercise training (AEXT) on the anti-inflammatory biomarker interleukin-10 (IL-10), the inflammatory biomarkers interleukin-6 (IL-6) and C-reactive protein (CRP), the endothelial activation marker CD62E+ endothelial microparticle (EMP), and the vasodilatory biomarker nitric oxide (NO) in an African American cohort. A secondary purpose was to conduct a complementary in vitro study on the influence of IL-10 and laminar shear stress (LSS) on African American endothelial cells. In Vivo Methods: The subjects were sedentary, putatively healthy, 45-71 y/o African American men and women. A pre-post study design was employed with baseline and post-intervention evaluations of office blood pressure, fasting blood sampling, and graded exercise testing. Subjects engaged in AEXT three times per week for six months at an intensity equivalent to 65% of their VO2max. Plasma concentrations of IL-10 and IL-6 were determined using an enzyme-linked immunosorbent assay. Levels of nitric oxide metabolites (NOx) were determined using a modified Griess assay. Plasma samples for CRP were sent to Quest Diagnostics Inc. for analysis. Circulating CD62E+ EMPs were quantified using a flow cytometer. In Vitro Methods: Human umbilical vein endothelial cells (HUVEC) from an African American donor were cultured and exposed to four experimental conditions: Static, Static with IL-10 Incubation, LSS at 20 dynes/cm2, and LSS at 20 dynes/cm2 with IL-10 Incubation. Western blotting experiments were conducted to measure endothelial nitric oxide synthase (eNOS) protein expression and its phosphorylated form (p-eNOS) at Serine 1177 in the cells in all four conditions. A modified Griess assay was used to measure NOx in the cell culture supernatant. In Vivo Results: There was a significant increase in NO (n=24; p=0.002), a significant decrease in IL-6 (n=32; p=0.04), a significant decrease in CRP (n=37; p=0.01), and a significant decrease in CD62E+ EMPs (n=28; pIn Vitro Results: Protein expression levels of both eNOS and p-eNOS were significantly increased in the LSS at 20 dynes/cm2 and LSS at 20 dynes/cm2 with IL-10 Incubation experimental conditions when compared to the Static experimental condition. NO concentration levels were significantly increased in the LSS at 20 dynes/cm2 and LSS at 20 dynes/cm2 with IL-10 Incubation experimental conditions when compared to the Static experimental condition. Conclusion: Based on these results, AEXT may be a viable, non-pharmacologic method to improve vascular inflammation status and vasodilation, and thereby contribute to reduced hypertension and cardiovascular disease risk in African Americans.