THE INFLUENCE OF AEROBIC EXERCISE TRAINING ON BIOMARKERS OF ENDOTHELIAL ACTIVATION IN SEDENTARY AFRICAN AMERICANS

Abstract

Purpose: Clinical, epidemiological and basic research evidence supports the inclusion of regular physical activity as a tool for the prevention of chronic disease and the enhancement of overall health. Cardiovascular disease (CVD), the number one cause of death in the United States, is more prevalent in African Americans when compared to other races. Extensive data suggests that increasing physical activity level, particularly with aerobic exercise training (AEXT), can improve modifiable risk factors (hypertension, obesity, dyslipidemia) for CVD. The common pathology for cardiovascular (CV) risk factors is atherosclerosis. Central to the complex pathology of atherosclerosis is the vascular endothelium. In recent years, autocrine and paracrine endothelial biomarkers that directly affect endothelial status (activated vs. inactivated) have been implicated in the pathogenesis of the development and progression of CVD and its precursors. Exercise interventions have been used to modify the concentrations of endothelial biomarkers in populations with varying disease states. The purpose of this study was to identify plasma and urinary biomarkers that are associated with aerobic capacity (VO2max) in a sedentary African American population and further determine the effect of 6-months of AEXT on the concentration and activity of the biomarkers. Methods: Participants were recruited from the Philadelphia, PA area. Twenty two pre-hypertensive African Americans (SBP 122.15±10.33, DBP 77.00±5.88; 52.27±6.25 years of age) were included. Routine fasting blood samples were drawn to assess blood lipids and fasting blood glucose along with urinalysis to rule out kidney dysfunction or disease. Subjects had a physical examination and BP measured under standardized conditions. Exclusion criteria included smoking, a body mass index (BMI) > 40 kg/m2, alcohol intake of more than 3 drinks per day, diabetes (fasting glucose level >126 mg/dl), total cholesterol >240 mg/dl, renal or CV disease. On a separate day, a sub-maximal graded exercise test with gas analysis was conducted to determine aerobic capacity. VO2max was estimated from the baseline submaximal graded exercise test. Regression analysis was used to calculate VO2max. Participants underwent 6 months of AEXT at a prescribed 3 sessions per week for 40 minutes at 65% VO2max. Plasma biomarkers of oxidative stress (8-isoprostane PGF2a), cellular activation (VCAM-1), anti-oxidants (SOD), vascular tone (NO) and anti-thrombosis (2,3 dinor 6-keto Prostaglandin F1a) were measured before and after AEXT by commercially available EIA and ELISA kits. CRP, a biomarker of systemic inflammation and predictor of CV events was assessed. Results: Estimated VO2max values confirmed that the exercise group was untrained (VO2max: 25.31 ± 3.91 ml/kg/min). At baseline the most significant correlations observed were between VO2max and CRP (r= -.50, p= .01) as well as CRP and 8-isoprostane PGF2a (r= .88, p2max and CRP remained statistically significant (r= -.46, p= .02). Nitric oxide and VCAM-1 concentrations significantly differed following the AEXT intervention (NO: pre 24.07 ± 8.80 µmol/L, NO: post 37.17 ± 15.57 µmol/L, p Conclusions: Elevated basal plasma VCAM-1, CRP and 8- isoprostane PGF2α levels are evidence of endothelial activation and systemic inflammation. Pre-intervention findings provide evidence that having a higher VO2max was strongly associated with decreased concentrations of CRP, a marker of systemic inflammation that is highly associated with risk for CVD. Post-intervention analysis suggests 6-months of AEXT is an appropriate intervention for elevating NO and decreasing VCAM-1 concentrations. This suggests there were cardioprotective modifications in the endothelial phenotype. The absence of significant change in SOD activity, 2,3 dinor 6-keto Prostaglandin F1a and CRP concentrations may suggest that AEXT is not a suitable mechanism to elicit improvements in all metabolic pathways that impact the state of the endothelium in previously sedentary African Americans.