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. In recent years,
we have found that air pollutant chemicals such as those present
in diesel exhaust particles are able to synergize with oxidized
phospholipids generated within oxidized LDL, in the promotion of
proatherogenic genes in vascular endothelial cells. We have also
determined that inhalation of ambient ultrafine particles lead
to systemic prooxidant and proinflammatory effects that result
in the development of dysfunctional HDL and enhancement of
atherosclerotic lesions.
-
Biology of vascular oxidative stress: We are interested
in genes and pathways of relevance in the oxidative stress
generated in vascular inflammatory entities such as
atherosclerosis, ischemia reperfusion and cardiac allograft
rejection response. We have determined that heme oxygenase-1
(HO-1) is an important antioxidant and anti-inflammatory
protective gene and together with its transcriptional regulator
Nrf2, they 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.
There is an important cross-talk 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: 589-96. |
