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METABOLOMICS OF BLOOD BIOMARKERS OF HYPERTENSION: EFFECT OF SUPERVISED EXERCISE TRAINING IN BLACK AMERICANS

Abstract

BACKGROUND: Black Americans (BAs) have a significant burden of hypertension (HTN) and endothelial dysfunction (EnDy) is one established mechanism of the elevated HTN burden in BAs. Blood pressure (BP) regulation occurs through integration of multiple physiological systems and behaviors (e.g., exercise). The focus of our lab is to discover exercise-adaptable biomarkers of gut microbial metabolism that might be epigenetic regulators of EnDy. Purpose: To evaluate blood metabolites associated with BP status (normal vs. HTN) and in 12 subjects after 8 weeks of supervised aerobic exercise that promoted a significant reduction in resting BP in BAs with HTN. METHODS: The present work implemented untargeted metabolomics (mass spectrometry) of fasted blood samples (serum) in BA subjects with and without HTN and after 8 weeks of exercise in BAs with HTN. RESULTS: Although manually recorded resting systolic BP was significantly lower after 8 weeks of exercise, 24-hr ambulatory BP was not significantly lower. Further, we report the top 5 metabolic pathways associated with HTN status, with the strongest associations shown with Vitamin A (retinol) metabolism, sex hormone biosynthesis and metabolism, pentose phosphate pathway, and de novo fatty acid biosynthesis. Further, an OPLS-discriminant analysis recognized a clear separation of individuals with and without HTN and between time points after 8 weeks of exercise training (T1-pre, T3-8 week). Analysis is ongoing to define biomarkers associated with the exercise-induced reduction in resting BP and gut microbiome characteristics. SIGNIFICANCE: Our initial results highlight a novel relationship between retinal/lipid signaling in HTN in BA. As we work through the analysis of these data, we expect to identify additional metabolites and translate our findings by investigating the metabolite’s role in endothelial cell function (epigenetic regulation) and the reversal and/or promotion of EnDy (in vitro).

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