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PM2.5 from Fracking Operations Induces Microvascular and Mitochondrial Dysfunction

水力压裂作业中的 PM2.5 会导致微血管和线粒体功能障碍

基本信息

批准号：
9304708
负责人：
TRAVIS LEE KNUCKLES
金额：
$ 45万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9304708
关键词：
Address Aerosols Affect Air Pollutants Alpha Particles Anatomy Animal Model Animals Apoptotic Aromatic Polycyclic Hydrocarbons Autopsy Basic Science Biochemistry Biological Availability Blood Vessels Blood flow Caliber Cardiac Cardiovascular Physiology Cardiovascular system Cell physiology Clinical Research Communities Complex Mixtures Development Disease Endothelial Cells Endothelium Engine Exhaust Environmental Exposure Environmental Pollution Epidemiology Exposure to Failure Federal Government Forearm Fracture Functional disorder Future Gases Geology Goals Health Health Hazards Heart failure Hypertension Impairment Individual Ischemia Knowledge Laboratories Link Local Government Lung Measurement Mediating Microcirculation Microscopy Microvascular Dysfunction Mission Mitochondria Morbidity - disease rate Natural Gas Nature Nerve Nitric Oxide Outcome Particulate Matter Pattern Performance Phase Physiological Policies Process Production Public Health Rattus Regulation Reperfusion Therapy Research Sampling Scientific Advances and Accomplishments Signal Transduction Silicon Dioxide Site Source State Government Students Surface Technology Testing Tissues Toxic effect Toxicology United States National Institutes of Health Vasodilation Work anthropogenesis cardiovascular health cardiovascular injury community intervention constriction epidemiology study fine particles functional decline innovation insight mitochondrial dysfunction mortality operation particle exposure pro-apoptotic protein protective effect protein expression reactive hyperemia respiratory toxicant ultrafine particle volatile organic compound

项目摘要

The production of shale gas, and the development of wells using horizontal drilling and hydraulic fracturing technology, is a major driver of the U.S. economy. The process of preparing well pads to completion of the work creates a complex mixture of airborne toxicants that includes elevated concentrations of particulate mat- ter (PM), ultrafine particles (UFPs) from diesel engine exhaust (DEE), silica, as well as volatile organic com- pounds (VOCs) and polyaromatic hydrocarbons from geological, surface and anthropogenic sources. The to- tality of materials that the individuals are exposed to is alarming to federal, state and local governmental organ- izations. Indeed, communities that are proximal to unconventional natural gas development (UNGD) well sites have greater health effects compared to communities without UNGD. However, what is not known is how ac- tive UNGD precipitates these health effects. PM, specifically fine PM (<2.5 µm in diameter, PM2.5) is a known cardiovascular toxicant. Several studies have demonstrated a significant impairment in vascular, and micro- vascular function. Combined, these studies indicate significant cardiovascular health effects even at low ambi- ent levels. Moreover, we have shown cardiac mitochondrial impairment, a significant contributor to progression of heart failure, following ambient PM exposure. However, what is not known is the relative toxicity of specific sources (source apportionment) or the mechanisms of cardiovascular injury following pulmonary PM2.5 expo- sure. The long-term goal is to establish physiologic mechanisms that explain the epidemiological health pat- terns during UNGD. The objective for this R15 application is to substantially advance the scientific understand- ing of the mechanisms that link pulmonary UNGD PM2.5 to remote tissue dysfunction. The central hypothesis is that pulmonary exposure to PM2.5 collected on-site during hydraulic fracturing will have greater microvascular and mitochondrial dysfunction, characterized by disturbances in mechanisms supporting normal arteriolar con- striction, endothelium-dependent dilation, mitochondrial function, and pro-apoptotic protein expression leading to cardiac functional declines. This hypothesis will be tested by 1) identifying the mechanistic alterations in mi- crovascular and mitochondrial function during different stages of UNGD, 2) identifying the cardiac functional declines that result from microvascular and mitochondrial dysfunction. The rationale for this work is that pro- posed research will add substantially to the mechanistic insights of PM2.5-induced microvascular and mito- chondrial dysfunction, while supporting our mission to educate and prepare students. Utilizing students to test theses aims will allow the students to gain knowledge in microscopy, necropsy, anatomy, biochemistry, and microvascular and cardiovascular physiology. The research proposed is innovative because it directly deter- mines toxicity of the complete matrix of toxicants produced during three phases of UNGD. The proposed re- search is significant as it will assess cardiovascular toxicity during different phases of drilling as well as mech- anisms of dysfunction that will bridge the gap between basic science and epidemiological UNGD health effects.

页岩气的生产，以及水平井钻井和水力压裂井的开发