The main research interest of our lab are focused on two areas of investigation:
Environmental Cardiology: we are dissecting the mechanism 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 particlare are able to synergize with oxidized phospholipids generated within oxidated LDL, in the promtion of proatherogenic genees in vascular endothelial cells. We have also determined that inhalation of ambient ultrafine particle lead to systemic prooxidant and proinflammatory effects that result in the development of dysfunctional HDL and enhancement of atheroscleorotic leisons.
Biology of vascular oxidative stress: we are interested in genes and pathways of relevence in the oxidative stress generated in vascular inflammatory entities such as atherosclerosis and ischemia reperfusion. We have determined that heme oxygenase-1(HO-1) is an important antioxidant and anti-inflammatory protective gene and together with transcriptional regulator Nrf2, they may play a central role in orchestrating the antioxidant defense of vascular cells. However, while HO-1 is anti-atherogenic gene, NrF2 promotes atherosclerosis instead partly due to the regulation of genes involved in lipid metabolism and cholesterol transport. This underscores the complextiy of reactive oxygen species (ROS) signaling in vascular cells. We are currently studying how HO-1 expression modulates variosu inflammatory pathways via the use of genetic and biochemical approaches.
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.