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

压力和交通相关空气污染对心血管健康的协同效应

• 批准号: 10560427
• 负责人: CHAO-YIN CHEN
• 金额: $ 75.76万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560427
• 关键词: Acute; Address; African American population; Air; Air Pollution; American; Animal Model; Animals; Biological; Biological Markers; Blood Pressure; Bronchoalveolar Lavage Fluid; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Chemicals; Chronic; Chronic stress; Circulation; Communities; Complex; Disparity; Duct (organ) structure; Electrocardiogram; Endocrine; Engineering; Environmental Epidemiology; Environmental Pollution; Epidemiology; Exposure to; Gases; Health; Human; Hydrocortisone; Immune; In Vitro; Inflammation; Intervention; Lead; Light; Literature; Maps; Measures; Mechanics; Mediating; Metabolic; Modeling; Oxidative Stress; Particle Size; Pathway interactions; Persons; Physiological; Policies; Pollution; Population; Poverty; Predisposition; Rattus; Reduce health disparities; Regulation; Research Personnel; Risk; Rodent; Role; Science; Shapes; Sprague-Dawley Rats; Stress; Structure; System; Telemetry; Testing; Time; Tissues; United States National Institutes of Health; Violence; Vulnerable Populations; Work; acute stress; air filter; atmospheric sciences; biological adaptation to stress; cardiovascular health; cytokine; design; effective intervention; environmental health disparity; environmental justice; epidemiological model; ethnic health disparity; exhaust; health disparity; hypothalamic-pituitary-adrenal axis; improved; low socioeconomic status; marginalized community; particle; racial health disparity; resilience; response; restraint stress; scientific atmosphere; social; social stressor; stem; synergism; time use; traffic-related air pollution; underserved community

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.

摘要 心血管疾病（CVD）是美国的主要死亡原因，不成比例地影响到 较低的社会经济地位（SEP）-这种差异归因于对交通和运输的高度暴露， 相关的空气污染（TRAP）和慢性社会压力。许多流行病学和毒理学研究表明， 暴露于慢性压力会大大增加对TRAP的易感性，尽管现在越来越多的证据表明， 表明TRAP也可能强烈影响下丘脑-垂体-肾上腺（HPA）轴功能， 压力反应，使相互作用的方向性和解释复杂化。关键是要理清这些 两个模型，以开发更多的生物学基础的流行病学模型结构，并完善设计， 压力和污染的时空暴露度量。最终，这项工作将有助于更好地识别 这将有助于加强对易受感染人群的健康监测，并确定有效的干预措施，以改善健康状况，减少健康差距。 然而，这样做是具有挑战性的，因为压力和TRAP都是复杂的暴露，具有多种多系统性。 影响。应激强烈影响免疫、内分泌和代谢功能，但影响程度很高。 时间敏感，因为急性和慢性压力表现非常不同。TRAP是一种高度复杂的化学物质混合物， 每一种都有不同的生理影响。在这个ViCTER提案中，我们建立了一个跨学科团队， 量化和比较慢性和急性应激、TRAP及其多种相互作用， 功能我们是独一无二的准备映射这一未探索的地形，作为完成高级调查员， 大气科学和机械工程（Wexler），心血管调节和自主神经功能 （陈），和暴露科学和社会环境流行病学（Cloughman）。为此，我们将使用 独特的TRAP输送系统，具有实时浓度和化学成分测量功能， 在大鼠中产生慢性和急性应激反应的模型，心血管的时间分辨测量 功能（遥测），以及慢性和急性应激标志物在多个时间点的生物学概况（例如， 皮质醇、CRP、细胞因子），以量化和比较上述两个概念模型中的方向性。 我们假设：（1）TRAP成分（轻型与重型车辆）不同地影响心血管 （2）在研究过程中，慢性应激可增强动物对TRAP的心血管反应; (3)TRAP可能损害动物对应激挑战的心血管弹性。这项研究将建立一个 一个具有互补专长的跨学科小组，研究压力之间相互作用的复杂性， 污染暴露-这一问题与服务不足和边缘化群体的健康差距有着深刻的关系 社区，特别是CVD，死亡的主要原因。团队将共同努力整合成果 这三个目标转化为后续R 01应用的假设。