Associations between the neural-hematopoietic-inflammatory axis and DNA methylation of stress-related genes in human leukocytes: Data from the Washington, D.C. cardiovascular health and needs assessment

Abstract

Chronic stress is associated with cardiovascular disease (CVD) risk and elevated amygdala activity. Previous research suggests a plausible connection between amygdala activity, hematopoietic tissue activity, and cardiovascular events; however, the underlying biological mechanisms linking these relationships are incompletely understood. Chronic stress is thought to modulate epigenomic modifications. Our investigation focused on associations between amygdala activity (left (L), right (R), maximum (M), and average (Av) AmygA), and splenic (SpleenA), and bone marrow activity (BMA) as determined by ¹⁸Fluorodeoxyglucose (FDG) on Positron Emission Tomography/Computed Tomography (PET/CT) scans. Subsequently, we assessed how these markers of chronic stress and hematopoietic activity might relate to the DNA methylation of stress-associated genes in a community-based cohort of African American individuals from Washington D.C. at risk for CVD. To assess the relationships between AmgyA, SpleenA, BMA, and DNA methylation, linear regression models were run and adjusted for body mass index and 10-year predicted atherosclerotic CVD risk. Among 60 participants (93.3% female, mean age 60.8), M-AmygA positively associated with SpleenA (β = 0.29; p = 0.001), but not BMA (β = 0.01; p = 0.89). M-AmygA (β = 0.37; p = 0.01 and β = 0.31; p = 0.02, respectively) and SpleenA (β = 0.73; p < 0.01 and β = 0.59; p = 0.005, respectively) were associated with both IL-1β and TNFα. Decreased M-AmygA, SpleenA, IL-1β, and TNFα were associated with methylation of NFκB1 at cg07955720 and STAT3 at cg19438966. Our findings suggest a potential association between AmygA, SpleenA, and pro-inflammatory cytokines in the setting of chronic stress, suggesting an adverse hematopoietic effect. Furthermore, findings reveal associations with epigenetic markers of NFκB and JAK/STAT pathways linked to chronic stress.