Grantee Research Project Results

Novel Markers of Air Pollution-induced Vascular Toxicity

EPA Grant Number: R833990
Title: Novel Markers of Air Pollution-induced Vascular Toxicity
Investigators: Campen, Matthew J. , Lund, Amie K.
Institution: Lovelace Biomedical & Environmental Research Institute
Current Institution: Lovelace Biomedical & Environmental Research Institute , New Mexico State University - Main Campus
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2008 through October 31, 2011 (Extended to October 31, 2012)
Project Amount: $500,000
RFA: Development of Environmental Health Outcome Indicators (2007) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Air Toxics

Objective:

Over the past decade, it has become clear that air pollution has an important impact on cardiovascular disease, especially on those outcomes where atherosclerosis, an inflammatory disease of arteries, plays a significant role. We have been developing a model over the past few years focused on a molecular pathway that may well link both chronic growth and development of atherosclerotic plaques, as well as the eventual destabilization and rupture, which is the precipitating event in infarction, stroke, and aneurysm. This pathway relates to the regulation of vascular gelatinases via induction by oxidatively modified lipids.

Several markers of atherosclerosis have been investigated in humans exposed under controlled conditions to particulate matter (PM), ozone (0₃), or diesel exhaust (DE). These include lL-6. C-reactive protein (CRP). and tumor necrosis factor-alpha (TNF-α), among others. Many of these markers have good specificity with chronic aerial inflammatOry disease but are otherwise uncharacterized for acute exposure (0 airborne pollutants. That is, there is no a priori reason to assume that pollutants act through these markers, especially acutely.

Approach:

The biological markers of vascular disease that we propose to investigate are based on genomic data that led to subsequent mechanistic investigations and finally to the testing of several potential lead markers in the plasma using murine models. For the present study, we propose to further characterize related molecular alterations in mouse models and then to confirm important findings in plasma from humans that have been exposed to DE under controlled conditions. For these studies, the plasma has already been generously donated by Dr. Mike Madden of the U.S. EPA Human Studies Division.

In Specific Aim 1, we will assay hypothesized markers in plasma and aortic tissue from mice exposed to various pollutant atmospheres. These studies will link the plasma markers with their mechanistic origins.

In Specific Aim 2, we will test the role of LOX-1 and CD36 scavenger receptors in mediating the vascular effects of inhaled pollutants. We hypothesize that oxidatively modified phospholipids may be a link between the lung and systemic circulation; scavenger receptors are the likely mediating intermediary.

In Specific Aim 3, we will use the information obtained in Specific Aims 1 and 2 to develop hypotheses for protein or biochemical markers to test in human plasma. We will first test the markers in murine samples and then confirm the relevance in human plasma.

Expected Results:

The results of this project should be a handful of biological markers that can be subsequently used to: 1) identify susceptible individuals, 2) identify causal components of the complex air pollution mixture, and 3) better understand the biological mechanisms involved in air pollution-induced cardiovascular toxicity.

Publications and Presentations:

Publications have been submitted on this project: View all 9 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 6 journal articles for this project

Supplemental Keywords:

particulate matter, nitrogen dioxide, carbon monoxide,, RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, chemical characteristics, human health effects, cardiovascular vulnerability, biological mechanisms, chemical composition, biological mechanism , human exposure, ambient particle health effects, autonomic dysfunction, oxidative stress

Progress and Final Reports:

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.