Remote Microvascular Dysfunction After Particulate Matter Exposure

颗粒物暴露后的远程微血管功能障碍

• 批准号: 7486839
• 负责人: Timothy R Nurkiewicz
• 金额: $ 47.72万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486839
• 关键词: Acute; Adhesions; Affect; Age; Air Pollutants; Air Pollution; Airborne Particulate Matter; Arginine; Arteries; Biological; Biological Availability; Blood; Blood Circulation; Blood flow; Bone Marrow; Cardiovascular Diseases; Cardiovascular system; Cells; Civilization; Cosmetics; Deposition; Development; Diesel Exhaust; Disruption; Endothelium; Etiology; Event; Exposure to; Female; Functional disorder; Gender; Gender Role; Health; Heart; Human; In Vitro; Incidence; Inflammatory; Investigation; Laboratories; Leukocytes; Life; Link; Lung; Measures; Microcirculation; Morbidity - disease rate; Mus; Muscle; Myocardium; Nanotechnology; Nitric Oxide; Nitrogen; Outcome; Oxidative Stress; Oxygen; Paint; Particulate Matter; Pathologic; Peripheral Resistance; Peroxidase; Pollution; Population; Prevention; Principal Investigator; Proteins; Rattus; Regulation; Reporting; Research Personnel; Resistance; Respiratory System; Risk; Severities; Skeletal Muscle; Solid; Source; Techniques; Testing; Tissues; Ultrafine; base; brachial nutrient artery; clinically relevant; day; environmental toxicology; improved; in vivo; insight; intravital microscopy; male; mortality; nanometer; nanoparticle; particle; pollutant; prevent; programs; research study; titanium dioxide; ultrafine particle

DESCRIPTION (provided by applicant): Epidemiological evidence indicates that acute pulmonary exposure to airborne pollutants such as particulate matter (PM) increases the risk of pulmonary and cardiovascular morbidity and mortality. This implies that PM affects extra-pulmonary tissues, as evidenced by the occurrence of cardiovascular dysfunction on high pollution days. Furthermore, Federal Criteria Documents for PM have provided a wealth of evidence demonstrating PM dependent effects on the cardiovascular system. However, despite its obvious importance in regulating the delivery of cells and molecules to all tissues, and in the etiology of most cardiovascular diseases, the Principal Investigator's laboratory conducts the lone investigations that explore how systemic microvascular function is affected by pulmonary PM exposure. The overall aim of this project is to determine if there is a true causal link between the inflammatory events that follow PM exposure and the disruption of endothelium-dependent dilation. The central hypothesis is: Inflammatory mechanisms govern the systemic microvascular dysfunction that follows ultrafine PM exposure, and the severity of this dysfunction is augmented in clinically relevant populations. Intravital microscopy and isolated vessels will be used to test this hypothesis in the spinotrapezius muscle, bone marrow, and subendocardial circulations of rats and mice exposed to diesel exhaust particles (DEPs) or ultrafine titanium dioxide. The role of gender and age in determining the severity of these effects will also be studied. Various in vivo and in vitro techniques will be used to measure microvascular reactivity after PM exposure, and to characterize pathological changes at this crucial level of the circulation. DEPs are mobile source emission air pollutants representative of particles that humans are exposed to on a regular basis. Ultrafine titanium dioxide is a commonly used nanoparticle found in cosmetics, paints and various protective coatings. A better understanding of how these particles affect remote microvascular function will provide mechanistic insight into pathologic changes that contribute to cardiovascular morbidity and mortality. Moreover, these studies may provide a biological basis for the epidemiological associations between air pollution and cardiovascular dysfunction. A fundamental understanding of these mechanisms is vital to the prevention and treatment of life-threatening cardiovascular events, and will contribute to control strategy development.

描述（由申请人提供）： 流行病学证据表明，急性肺暴露于空气污染物（例如颗粒物（PM））会增加肺部和心血管发病率和死亡率的风险。这意味着PM会影响肺外组织，这是在高污染日发生心血管功能障碍的情况所证明的。此外，PM的联邦标准文件提供了大量证据，证明了对心血管系统的依赖性影响。然而，尽管在调节细胞和分子向所有组织的递送以及大多数心血管疾病的病因学方面具有显而易见的重要性，但首席研究者的实验室仍进行了孤独的研究，以探索探索系统的微血管功能如何受到肺部PM暴露的影响。该项目的总体目的是确定PM暴露后的炎症事件与内皮依赖性扩张的破坏之间是否存在真正的因果关系。中心假设是：炎症机制控制超铁PM暴露后的全身微血管功能障碍，并且这种功能障碍的严重程度在临床上相关的人群中增加了。插入式显微镜和分离的血管将用于检验该假设，该假设在大鼠和暴露于柴油排气颗粒的大鼠和小鼠的骨髓骨髓和心内膜下循环中进行检验。性别和年龄在确定这些影响严重程度方面的作用也将得到研究。各种体内和体外技术将用于测量PM暴露后的微血管反应性，并在循环的这种关键水平下表征病理变化。 DEP是代表人类定期暴露的颗粒的移动源排放空气污染物。 Ultrafine Titanium二氧化钛是一种在化妆品，油漆和各种保护性涂层中发现的常用纳米颗粒。更好地理解这些颗粒如何影响远程微血管功能将提供对病理变化的机械洞察，从而有助于心血管发病和死亡。此外，这些研究可能为空气污染与心血管功能障碍之间的流行病学关联提供生物学基础。对这些机制的基本理解对于预防和治疗威胁生命的心血管事件至关重要，并将有助于控制战略发展。