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; 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.

抽象的 心血管疾病（CVD）是美国的主要死亡原因，不成比例地影响 较低的社会经济地位（SEP） - 差异归因于对这两种交通的暴露量加强 - 相关的空气污染（陷阱）和慢性社会压力源。许多流行病学和毒理学研究表明 这种暴露于慢性压力可以极大地增加对陷阱的敏感性，尽管现在越来越多的证据 表明陷阱也可能会强烈影响下丘脑 - 垂体 - 肾上腺（HPA）轴功能和急性 压力反应，使相互作用的方向性和解释复杂化。将这些解开至关重要 两种模型，以开发更具生物学的流行病学模型结构，并完善 应力和污染的时空暴露指标。最终，这项工作将有助于更好地识别 易感人群，并确定有效的干预措施以改善健康并减少健康差异。 但是，这样做是具有挑战性的，因为压力和陷阱都是与潜水员多系统的复杂暴露 影响。压力显示出强烈影响免疫，内分泌和代谢功能，但影响很高 时间敏感，因为急性和慢性应激的表现非常不同。陷阱是化学物质的高度复杂的混合物， 每个都有非常不同的生理影响。在这个Victer的建议中，我们建立了一个跨学科团队 量化和比较慢性和急性应力，陷阱及其多个相互作用，以塑造心血管 功能。正如有成就的高级调查员 大气科学与机械工程（韦克斯勒），心血管调节和自主功能 （陈）和暴露科学和社会环境流行病学（Clougherty）。为此，我们将使用 具有实时浓度和化学组成措施的独特陷阱输送系统，这是一个验证的 用于在大鼠中产生慢性和急性应力反应的模型，心血管的时间分辨测量 慢性和急性应力标记的功能（遥测）和生物学分析（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）陷阱组成（轻 - 与重型车辆）的影响不同 功能; （2）在研究过程中，慢性压力可能会增强动物对陷阱的心血管反应； （3）陷阱可能会损害动物对压力挑战的心血管韧性。这项研究将建立一个 具有完善专业知识的跨学科团队，以检查压力之间的互动中的复杂性 和污染暴露 - 一个与服务不足和边缘化的健康分配非常相关的问题 社区，特别是对于CVD，是死亡的主要原因。团队将共同努力以整合结果 在这三个目标中，旨在用于随后的R01应用的假设。