- Project 3
Diesel Exhaust, Vascular Response, and Systemic Inflammation
- The association between exposure to ambient particulate matter (PM) air pollution and cardiovascular morbidity and mortality is well established. In urban areas a growing body of literature indicates an association between exposure to traffic-related air pollution and both acute and chronic cardiovascular health effects. Acute coronary syndrome, arrhythmias and heart failure have all been linked to exposure to traffic-related air pollution.
Diesel exhaust particles is an important and predominant ultrafine component of urban airborne particles. Exposure to ambient PM causes a pro-inflammatory systemic response that includes an increase in circulation mediators and activation of the bone marrow to release leukocytes and platelets. Several of these circulating pro-inflammatory mediators (IL-1β, IL-6 & CRP) are known to activate endothelium that facilitates platelet adherence and leukocyte recruitment in to blood vessel walls promoting blood vessel disease.
The endothelium is the key interface protecting and controlling vascular responses and activation and dysfunction of this protective barrier is pivotal in blood vessel functional responses, the initiation, development and progression of atherosclerosis (AS) and stability of atherosclerotic plaques.
The general hypothesis of our project is that diesel exhaust particle (DEP) exposure induces a systemic inflammatory response and circulating mediators of this response activate vascular endothelium resulting in abnormal functional vascular responses. Our project will test the following specific aims:
1: To examine the relationship between lung inflammation, systemic inflammation and vascular responses induced by exposure to DEP.
2: To determine the mechanism of heightened vascular contraction and impaired endothelium-dependent dilation following diesel exhaust exposure.
3: To test whether impaired endothelial insulin signaling and NO production are associated with IDDB activation in vivo during exposure to DEP.
Director: Kanchan Chitaley, PhD
Francis Kim, MD
Stephan van Eeden, MD, PhD