This is a revised version of an application originally submitted in response to RFA #HL-96-018. The proposal is aimed at testing the hypothesis that homocysteinemia contributes to the development of atherosclerosis primarily by altering the cellular functions of inflammatory cells. The application consists of two Specific Aims. Under the first, the investigator will determine whether plasma homocysteine (HC) stimulates an increased fibroproliferative response in vivo in hypercholesterolemic mice with homocysteinemia.
Under Aim 2, the investigator will determine the mechanism by which HC and lipid accumulation alter glutathione and NADH/NADPH metabolism, thereby activating macrophages in vitro.
|Bea, Florian; Hudson, Francesca N; Neff-Laford, Haley et al. (2009) Homocysteine stimulates antioxidant response element-mediated expression of glutamate-cysteine ligase in mouse macrophages. Atherosclerosis 203:105-11|
|Shultz, Jennifer M; Zhu, Xiao Dong; Knopp, Robert H et al. (2004) Norgestimate and medroxyprogesterone acetate do not attenuate the atheroprotective effects of 17beta-estradiol in ovariectomized, apolipoprotein E-deficient mice. Fertil Steril 82 Suppl 3:1133-9|
|Bea, Florian; Hudson, Francesca N; Chait, Alan et al. (2003) Induction of glutathione synthesis in macrophages by oxidized low-density lipoproteins is mediated by consensus antioxidant response elements. Circ Res 92:386-93|
|Bea, Florian; Blessing, Erwin; Shelley, Monica I et al. (2003) Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis 167:187-94|
|Bea, Florian; Blessing, Erwin; Bennett, Brian J et al. (2003) Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis. Cardiovasc Res 60:198-204|
|Bea, Florian; Puolakkainen, Mirja H; McMillen, Timothy et al. (2003) Chlamydia pneumoniae induces tissue factor expression in mouse macrophages via activation of Egr-1 and the MEK-ERK1/2 pathway. Circ Res 92:394-401|
|Blessing, Erwin; Kuo, Cho-Chou; Lin, Tsun-Mei et al. (2002) Foam cell formation inhibits growth of Chlamydia pneumoniae but does not attenuate Chlamydia pneumoniae-induced secretion of proinflammatory cytokines. Circulation 105:1976-82|
|Bea, Florian; Blessing, Erwin; Bennett, Brian et al. (2002) Simvastatin promotes atherosclerotic plaque stability in apoE-deficient mice independently of lipid lowering. Arterioscler Thromb Vasc Biol 22:1832-7|