Curriculum Vitae
Research
Interest
The main research
interests of our laboratory are focused on two areas of
investigation:
-
Environmental Cardiology: We are
dissecting the mechanisms by which exposure to air particulate
matter promotes atherosclerosis and ischemic heart disease and
studying gene-environment interactions of relevance in the
development of cardiovascular disease. We have determined that
air pollutant chemicals such as those present in diesel exhaust
particles are able to induce inflammatory genes in endothelial
cells, in a synergistic fashion with oxidized phospholipids.
This synergy was also present in tissues harvested from animals
exposed to concentrated ambient ultrafine particles which are
the smallest (<0.18 µm) and most abundant particulate pollutants
in urban settings, responsible for the largest promotion of
atherosclerosis as compared with particles of bigger size. One
of the mechanisms how air pollution appears to promote
atherosclerosis is via the generation of dysfunctional HDL that
either loses its anti-inflammatory capacity or even becomes
proinflammatory.
-
Biology of vascular oxidative
stress: We are interested in genes and pathways of relevance in
the vascular oxidative stress generated in atherosclerosis and
cardiac allograft rejection response, such as heme oxygenase-1
(HO-1) and its transcription factor Nrf2. We have shown that
HO-1 is an important antioxidant and anti-inflammatory
protective gene that may play a central role in orchestrating
the antioxidant defense of vascular cells. We are currently
studying how is that HO-1 expression modulates various
inflammatory pathways via the use of genetic and biochemical
approaches. We have established a good complementation in
between our two areas of investigation as it appears that the
generation of reactive oxygen species in the vasculature and the
expression of Nrf2-regulated antioxidant genes represent
important elements in the systemic effects of air particulate
pollutants.
Representative Publications
Araujo JA,
Meng L, Tward A, Hancock WW, Zhai Y, Lee A, Iyer S, Buelow R,
Busuttil RW, Shih DM, Lusis AJ, Kupiec-Weglinski JW. Systemic
rather than local heme oxygenase-1 overexpression improves cardiac
allograft outcomes in a new transgenic mouse. J Immunol 2003: 171:
1572-80.
Tsuchihashi SI,
Livhits M, Zhai Y, Bussutil RW, Araujo JA, Kupiec-Weglinski
JW. Basal rather than induced HO-1 levels are crucial in the
antioxidant cytoprotection. J Immunol 2006, 177: 4749-57.
Orozco LD,
Kapturczak MH, Barajas B, Wang X, Weinstein MM, Wong J, Deshane J,
Bolisetty S, Shaposhnik Z, Shih D, Agarwal A, Lusis AJ, Araujo
JA. Heme oxygenase-1 expression in macrophages plays a
beneficial role against atherosclerosis. Circ Research 2007; 100:
1703-1711.
Gong KW, Zhao W, Li
N, Barajas B, Kleinman M, Sioutas C, Horvath S, Lusis AJ, Nel A,
Araujo JA. Air pollutant chemicals and oxidized lipids
exhibit genome wide synergistic effects on endothelial cells.
Genome Biology 2007; 8: R149.
Araujo JA,
Barajas B, Kleinman M, Wang X, Bennett B, Gong KW, Navab M,
Harkema J, Sioutas C, Lusis AJ, Nel A. Ambient particulate
pollutants in the ultrafine range promote early atherosclerosis
and systemic oxidative stress. Circ Research 2008; 102 (online
ahead of print). |
