Synergistic Effects of Stress and Traffic-Related Air Pollution on Cardiovascular Health

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ABSTRACT Cardiovascular disease (CVD), the leading cause of death in the U.S., disproportionately impacts persons of lower socioeconomic position (SEP) -- a disparity that has been attributed to heightened exposures to both traffic- related air pollution (TRAP) and chronic social stressors. Many epidemiologic and toxicologic studies have shown that exposures to chronic stress can vastly increase susceptibility to TRAP, though growing evidence now suggests that TRAP may also strongly impact hypothalamic-pituitary-adrenal (HPA)-axis function and acute stress response, complicating the directionality and interpretation of interactions. It is critical to disentangle these two models, to develop more biologically-grounded epidemiologic model structures, and refine the design of space-time exposure metrics for both stress and pollution. Ultimately, this work will help to better identify susceptible populations, and identify effective interventions to improve health and reduce health disparities. Doing so is challenging, however, as both stress and TRAP are complex exposures with diverse multi-systemic impacts. Stress is shown to strongly impact immune, endocrine, and metabolic function, but effects are highly time-sensitive, as acute and chronic stress manifest very differently. TRAP is a highly complex mix of chemicals, each with very different physiologic impacts. In this ViCTER proposal, we establish an interdisciplinary team to quantify and compare chronic and acute stress, TRAP, and their multiple interactions, in shaping cardiovascular function. We are uniquely poised to map this unexplored terrain, as accomplished senior investigators in atmospheric science and mechanical engineering (Wexler), cardiovascular regulation and autonomic function (Chen), and exposure science and social-environmental epidemiology (Clougherty). To do so, we will use a unique TRAP delivery system with real-time concentration and chemical composition measures, a well-validated model for generating chronic and acute stress responses in rats, time-resolved measures of cardiovascular function (telemetry), and biological profiling at multiple time points for chronic and acute stress markers (e.g., cortisol, CRP, cytokines), to quantify and compare directionality in the two conceptual models described above. We hypothesize that: (1) TRAP composition (light- vs. heavy-duty vehicles) differently impact cardiovascular function; (2) Chronic stress may heighten animals’ cardiovascular response to TRAP, over the course of study; (3) TRAP may compromise animals’ cardiovascular resilience to stress challenge. This study will establish an interdisciplinary team with complementary expertise to examine complexities in the interactions among stress and pollution exposures – an issue profoundly relevant to health disparities in under-served and marginalized communities, especially for CVD, the leading cause of death. The team will work together to integrate the results of the three aims into hypotheses for subsequent R01 applications.