Cardiovascular Effects of Particles:The Role of Oxidative Stress and Metal Pathw

描述（由申请人提供）：自20世纪80年代末以来，对急性和慢性暴露于颗粒空气污染的研究表明，颗粒空气污染与早死有关。很快就发现，这些早期死亡大多数是心血管疾病。定义潜在的机制，可以解释与暴露于环境颗粒物相关的心脏死亡率/发病率的流行病学调查结果，定义亚群的风险增加的不良健康结果的颗粒物，并了解不同类型的颗粒物的不同毒性是美国确定的研究重点。S.国家研究理事会。我们建议检查关联的不同类型和来源的颗粒暴露与心血管和肺反应沿着一个机械的途径，使用的数据从规范的老化研究，一个前瞻性队列研究进行的退伍军人管理局在大波士顿地区。具体来说，我们将研究是否在自动功能的短期变化，作为指标的心率变异性，与颗粒暴露，并确定是否通过检查基因型，修改防御氧化应激和金属处理的影响修改的氧化应激和金属毒性介导的影响。我们将类似地检查血管功能的关联和效应修饰，如通过动脉顺应性和血压的无创脉冲多普勒测量所指示的，并检查与炎症和氧化应激的全身标志物（c反应蛋白、Sicam、Svcam、同型半胱氨酸和8-羟基鸟苷）的直接关联。

DESCRIPTION (provided by applicant): Since the late 1980s, studies of acute and chronic exposure to particulate air pollution have shown it to be associated with early death. It was quickly apparent that most of these early deaths were from cardiovascular disease. Definition of the underlying mechanisms that may explain the epidemiological findings of cardiac mortality/morbidity associated with exposure to ambient particles, definition of subpopulation at increased risk of adverse health outcomes from particulate matter, and understanding the differential toxicity of different types of particles are among the research priorities defined by the U. S. National Research Council. We propose to examine the association of different types and sources of particle exposure with cardiovascular and pulmonary responses along a mechanistic pathway, using data from the Normative Aging Study, a prospective cohort study conducted by the Veterans Administration in the greater Boston area. Specifically, we will examine whether short term changes in automatic function, as indexed by heart rate variability, are associated with particle exposure, and determine whether that effect is mediated by part by oxidative stress and metal toxicity by examining effect modification by genotypes that modify defenses against oxidative stress and metal handling. We will similarly examine associations, and effect modification, for vascular function, as indexed by a non-invasive pulse Doppler measures of arterial compliance and blood pressure, and examine a direct association with systemic markers of inflammation and oxidative stress (c reactive protein, Sicam, Svcam, homocysteine, and 8-hydroxyguanosine.