Extramural Research
Presentation Abstract
Grantee Research Project Results
Howard Kipen1,2, Robert Laumbach1,2, Deborah
Laskin3, Paul Lioy1,2, Tina Fan1,2,
Claire Philipp1,Daniel Shindler1, Jim Zhang4, and
Pamela Ohman-Strickland4
1University of Medicine and Dentistry of New Jersey Robert
Wood Johnson Medical School,
Piscataway, NJ; 2University of Medicine and Dentistry of New
Jersey Environmental
and Occupational Health Sciences Institute, Piscataway, NJ; 3Rutgers
University,
Piscataway, NJ; 4University of Medicineand Dentistry of New
Jersey School
of Public Health, Piscataway, NJ
EPA Grant Number: R832144
Project Description:
Increased occurrence of unstable angina and myocardial infarction, particularly
in individuals vulnerable from preexisting atherosclerotic cardiovascular
disease (ASCVD), follow even hourly increases in particulate air pollution.
The mechanisms underlying these acute cardiovascular effects are unknown.
Thrombosis, closely related to endothelial cell dysfunction and platelet
activation, is now widely recognized to play an important role in acute
exacerbations of cardiovascular disease. In experimental studies, endothelial
changes are observed within minutes following a 2-hour exposure of humans
to inhaled particulate air pollution. Similarly, platelet activation and
thrombosis are observed in rodents within 30 minutes of intratracheal
instillation of various ultrafine particles. In these models, both the
endothelial and platelet responses appear to be independent of lung inflammation,
suggesting an immediate and direct effect of ultrafine particles on these
cells. The overall objective of our studies is to explore mechanisms mediating
particle-induced cardiovascular effects. We hypothesize that the acute
increase in risk of cardiac events following inhalation of ultrafine and
fine particles is mediated by a rapid and direct passage of the particles
from the lung into the blood, leading immediately to platelet activation
and endothelial dysfunction. Moreover individuals with genetically increased
risk for ASCVD and endothelial dysfunction will be more sensitive to the
effects of ultrafine and fine particles on the endothelium. To test this
hypothesis we will use pollutant models of freshly generated diesel exhaust
or a sec-ondary organic aerosol both of which consist predominately of
particles less than one micron in diameter. The effects of the two fine
and ultra fine aerosols will be compared in healthy individuals and individuals
with and without a genetic predisposition to endothelial cell dysfunction
and ASCVD.