Core B: Laboratory Testing Core The Testing Laboratory Core B has the goal to serve every project in the Program. It will provide an array of assays assessing fibrinolysis, coagulation, anticoagulant activities, and plasma lipid profiles. The Core will also provide assays of inflammatory cytokines, and adipokines as well as with established kits for mouse proteins associated with thrombosis, atherosclerosis and obesity. The specific assays that are available for each of the projects are indicated below. Core B will also coordinate the high through-put screening of small molecules by the Center for Chemical Genomics. Project 1: Core B will perform analysis of plasma PAI-1 levels for both active and inactive PAI-1 and of plasminogen activator antigen and activity levels. In addition, plasma lipid profiles will be routinely determined and immunoassays of various inflammatory cytokines as well as adipokines will be measured in a mutiplex format using the Luminex Technology. High through-put screening of small molecule compound libraries for the development of novel PAI-1 inactivating agents will also be performed through the Center for Chemical Genomics. Project 2: Core B will perform analysis of plasma PAI-1 levels for both active and inactive PAI-1 and of plasminogen activator antigen and activity levels. Murine plasmas will also be analyzed for increased risk for thrombosis by determining the levels of plasma coagulation, and anticoagulant proteins in various strains of mice at baseline, and after venous thrombosis with or without hypercholesterolemia. D-dimer levels will also be measured. Procoagulant microparticles will also be measured as well as immunoassays of various inflammatory cytokines. Project 3: Core B will assist the investigators off Project 3 by assessing platelet function including bleeding times and platelet aggregation in mice. Fibrinolytic parameters will be determined including PAI-1 and plasminogen activator levels. Immunoassays of various inflammatory cytokines will also be measured in a mutiplex format using the Luminex Technology. Project 4: Core B will assist the investigators of Project 4 by developing novel, assays for coagulation/fibrinolysis and platelet function in Zebrafish. These assays will include immunoassays and functional assays such as clotting times as well as factor assays. The overall goals of the Testing Laboratory Core B are to enhance the success of each individual project by providing rigorous, standardized assays and to ensure that the combined Program is stronger than each of its individual parts.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL089407-05
Application #
8375069
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$227,286
Indirect Cost
$69,924
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Wu, Jianbo; Strawn, Tammy L; Luo, Mao et al. (2015) Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling vascular endothelial growth factor receptor-2-αVβ3 integrin cross talk. Arterioscler Thromb Vasc Biol 35:111-20
Obi, A T; Diaz, J A; Ballard-Lipka, N L et al. (2014) Plasminogen activator-1 overexpression decreases experimental postthrombotic vein wall fibrosis by a non-vitronectin-dependent mechanism. J Thromb Haemost 12:1353-63
Diaz, Jose A; Alvarado, Christine M; Wrobleski, Shirley K et al. (2013) The electrolytic inferior vena cava model (EIM) to study thrombogenesis and thrombus resolution with continuous blood flow in the mouse. Thromb Haemost 109:1158-69
Li, Shih-Hon; Reinke, Ashley A; Sanders, Karen L et al. (2013) Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1. Proc Natl Acad Sci U S A 110:E4941-9
Patterson, K A; Zhang, X; Wrobleski, S K et al. (2013) Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects. Thromb Res 131:268-76
Shuster, Katherine A; Wrobleski, Shirley K; Hawley, Angela E et al. (2013) Prothrombotic effects of thrombolytic therapy in a rat (Rattus norvegicus) model of venous thrombolysis. Comp Med 63:244-51
Osterholzer, John J; Christensen, Paul J; Lama, Vibha et al. (2012) PAI-1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury. J Pathol 228:170-80
Fredriksson, Linda; Nilsson, Ingrid; Su, Enming J et al. (2012) Platelet-derived growth factor C deficiency in C57BL/6 mice leads to abnormal cerebral vascularization, loss of neuroependymal integrity, and ventricular abnormalities. Am J Pathol 180:1136-44
Visovatti, Scott H; Hyman, Matthew C; Bouis, Diane et al. (2012) Increased CD39 nucleotidase activity on microparticles from patients with idiopathic pulmonary arterial hypertension. PLoS One 7:e40829
Wang, Lingyan; Ly, Christine M; Ko, Chun-Ying et al. (2012) uPA binding to PAI-1 induces corneal myofibroblast differentiation on vitronectin. Invest Ophthalmol Vis Sci 53:4765-75

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