EFFECTS OF FOSSIL FUEL PARTICULATE MATTER ON CARDIAC FUNCTION

化石燃料颗粒物对心脏功能的影响

• 批准号: 8167809
• 负责人: MEI ZHANG
• 金额: $ 7.45万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167809
• 关键词: Acute; Air Pollution; Alveolar; Alveolar Macrophages; Arts; Blood Circulation; Caliber; Cardiac; Cardiac Myocytes; Cardiovascular system; Cell Survival; Computer Retrieval of Information on Scientific Projects Database; Congestive Heart Failure; Disease; Endothelium; Environment; Event; Fossil Fuels; Functional disorder; Funding; Goals; Grant; Health; Heart; Homeostasis; Hospitalization; Inflammatory; Institution; Insulin Resistance; Intervention; Ischemic Stroke; Molecular Biology Techniques; Morbidity - disease rate; Myocardial; Myocardial Infarction; Myocardial Ischemia; Obesity; Particulate Matter; Pathogenesis; Phagocytosis; Physiological; Research; Research Personnel; Resources; Risk; Role; Source; System; Therapeutic; Ultrafine; United States National Institutes of Health; Ventricular Arrhythmia; air contaminant; cardiovascular risk factor; endoplasmic reticulum stress; inhibitor/antagonist; insulin signaling; mortality; particle

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ambient air pollution is a major risk factor for cardiovascular morbidity and mortality. Short-term elevation in ambient particulate matter (PM) has been implicated in the pathogenesis of acute cardiovascular events including myocardial infarction, ventricular arrhythmias and ischemic stroke. A positive association has been identified between short-term increases in respirable or fine particles (particulate matter with aerodynamic diameter d10 ¿m (PM10) or d2.5 ¿m (PM2.5), respectively) and risk of hospitalization for congestive heart failure. The ultrafine PM is capable of directly entering systemic circulation through alveolar endothelium without having to go through phagocytosis of alveolar macrophages. These air contaminants may trigger a cascade of detrimental health effects involving cardiovascular and other systems through their pro-inflammatory effects. However, the precise mechanism of action behind long-term PM exposure-induced ischemic heart disease is essentially unknown. Ample evidence has implicated the essential role of endoplasmic reticulum (ER) stress in a number of environment-related disease conditions including obesity and insulin resistance. ER stress may directly induce compromised insulin signaling and cell survival although little information is available for the contribution from ultrafine PM air pollution. The central hypothesis of this proposal is that ultrafine PM directly triggers ER stress, compromised insulin signaling and impaired cardiac contractile function. We will employ state-of-the-art physiological and molecular biology techniques to evaluate the impact of ultrafine PM on ER stress, insulin signaling, intracellular Ca2+ homeostasis, and myocardial and cardiomyocyte contractile function, with or without intervention of ER stress inhibitors. Our long-term goal is to delineate the role of ER stress in the interplay between ambient particulate matter air pollution and cardiac dysfunction. Completion of this project should provide a therapeutic rationale for ER stress intervention for air pollution-associated heart problems.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 环境空气污染是心血管发病率和死亡率的主要危险因素。急性心血管事件的发病机理（包括心肌梗塞，心室心律不齐和缺血性中风）已经实施了环境颗粒物（PM）的短期升高。在呼吸或细颗粒的短期增加（分别具有空气动力学直径D10»M（PM10）或D2.5？m（PM2.5）的颗粒物之间，已经确定了正相关的阳性关联，以及用于充血性心力衰竭的住院风险。 Ultrafine PM能够直接通过牙槽园进入全身循环，而不必经过肺泡巨噬细胞的吞噬作用。这些空气污染物可能会通过其促炎作用引发一系列涉及心血管和其他系统的有害健康效应。然而，长期暴露于PM暴露引起的缺血性心脏病背后的精确作用机理本质上是未知的。充分的证据已经在许多与环境相关的疾病条件（包括肥胖和胰岛素抵抗）中实施了内质网（ER）应激的基本作用。 ER应激可能直接引起受损的胰岛素信号传导和细胞存活，尽管几乎没有信息可用于Ultrafine PM空气污染的贡献。该提案的中心假设是，Ultrafine PM直接触发ER应力，胰岛素信号传导和心脏收缩功能受损。我们将采用最先进的生理和分子生物学技术来评估Ultrafine PM对ER应激，胰岛素信号传导，细胞内CA2+稳态以及心肌和心肌细胞收缩功能的影响，或者在有或没有干预ER应力抑制剂的情况下。我们的长期目标是描述ER应力在环境特定物质空气污染和心脏功能障碍之间的相互作用中的作用。该项目的完成应为与空气污染相关的心脏问题提供治疗压力干预的治疗理由。