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Out of 350,000 sudden cardiac deaths each year in the United States, 60,000 deaths have been linked to air
pollution, suggesting a detrimental role of environmental pollutants in the development of cardiac toxicity.
Although epidemiology studies have associated exposure to particulate matter (PM) with acute mortality and
morbidity, only recently have they found associations between ozone and mortality. It has been challenging to
disentangle the toxic effects of ozone from those of PM in these studies because the 2 pollutants are often closely
correlated temporally and geographically. In studies using rats from controlled ozone (O
3
) exposure environment
we showed moderate and chronic cardiac dysfunction after 4 and 8 weeks of O
3
inhalation respectively. This
stage dependent O
3
-mediated progressive decline in cardiac function was associated with increasing levels
of inflammatory mediators. Our findings were cited and the results validated in a recent USEPA sponsored
human study where exposure to O
3
was shown to modulate the cardiovascular system by increasing the levels
inflammatory mediators. Later studies from our laboratory suggest a balance between caveolin-1 and caveolin-3
may play a role in O
3
associated cardiac toxicity. Since interaction of caveolins with p38MAPK is involved in
regulating death and survival signaling in the cardiac muscle, our recent findings in O
3
-exposed rats suggest a
stage dependent involvement of caveolin mediated p38MAPK associated death and survival signaling and that
more than one pathways may be involved in the pathology of O
3
-mediated cardiac toxicity.
Biography
Rajat Sethi received his Ph.D. from the Department of Medicine, University of Manitoba, Canada. He is currently the Chair of
Department of Pharmaceutical and Biomedical Sciences at the California Health Sciences University, Clovis, California. Prior to
this he served as the Assistant Dean for Research and Evidence Based Practice at the Texas A&M Health Science Center. He has
more than 100 publications in the field of cardiac pathology, holds 18 patents, has authored 7 books, and serves in the editorial
board for many journals. He received grants from federal, local agencies, and from various foundations. He has been an invited
speaker in many national and international meetings and is the recipient of numerous awards and honors for his contribution to
research and education.
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