This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016474-11
Application #
8359728
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$102,681
Indirect Cost
Name
University of Wyoming
Department
Type
Schools of Allied Health Profes
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
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