Core B, the Biochemistry, Pathology and Imaging Core will continue to serve all three Projects through all five years of the Program. The core is composed of three units: (1) The Biochemistry Unit of Core B will perform assays on tissue/plasma of mice and cultured cells in the individual projects for assessment of oxidative stress, AGEs and other biochemical mediators linked to RAGE and vascular dysfunction. (2) The Pathology Unit of Core B will perform pathological analysis of mouse tissues. This Unit will serve all 3 projects for standardization of immunohistochemistry and semiquantitative analyses. The Unit will perform analysis of atherosclerosis (aortas (atherosclerosis at the aortic root and en face assessment of aorta), angiogenesis (Project 2-3) and myocardial infarction size (Project 3). (3) The newly-formed Imaging Unit will perform novel imaging techniques using state-of-the-art new equipment for molecular imaging studies in atherosclerosis and apoptosis (Project 1) and angiogenesis (Project 2).

Public Health Relevance

Atherosclerosis, peripheral arterial disease and myocardial infarction and its consequences are highly prevalent diseases. In subjects with diabetes, the incidence and severity of these disorders is increased. This application focuses on the Receptor for Advanced Glycation Endproducts (RAGE) and its biology in accelerated cardiovascular disease, particularly in diabetes.

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National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Schmidt, Ann Marie (2014) Skin autofluorescence, 5-year mortality, and cardiovascular events in peripheral arterial disease: all that glitters is surely not gold. Arterioscler Thromb Vasc Biol 34:697-9
Song, Fei; Hurtado del Pozo, Carmen; Rosario, Rosa et al. (2014) RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice. Diabetes 63:1948-65
Vedantham, Srinivasan; Thiagarajan, Devi; Ananthakrishnan, Radha et al. (2014) Aldose reductase drives hyperacetylation of Egr-1 in hyperglycemia and consequent upregulation of proinflammatory and prothrombotic signals. Diabetes 63:761-74
Schmidt, Ann Marie (2014) Recent highlights of ATVB: diabetes mellitus. Arterioscler Thromb Vasc Biol 34:954-8
Manigrasso, Michaele B; Juranek, Judyta; Ramasamy, Ravichandran et al. (2014) Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol Metab 25:15-22
Kong, Linghua; Shen, Xiaoping; Lin, Lili et al. (2013) PKC* promotes vascular inflammation and acceleration of atherosclerosis in diabetic ApoE null mice. Arterioscler Thromb Vasc Biol 33:1779-87
Tekabe, Yared; Luma, Joane; Li, Qing et al. (2012) Imaging of receptors for advanced glycation end products in experimental myocardial ischemia and reperfusion injury. JACC Cardiovasc Imaging 5:59-67
Toure, Fatouma; Fritz, Gunter; Li, Qing et al. (2012) Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways. Circ Res 110:1279-93
Vedantham, Srinivasan; Noh, HyeLim; Ananthakrishnan, Radha et al. (2011) Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol 31:1805-13
Hofmann Bowman, Marion A; Fedson, Savitri; Schmidt, Ann Marie (2011) Advanced glycation end products in diabetic cardiomyopathy: an alternative hypothesis. J Heart Lung Transplant 30:1303; discussion 1303-4

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