The mouse is the most commonly used animal in biomedical research comprising >90% of all animal experimentation. This mammalian species is often the prime choice to flesh out mechanisms of action of drugs and to establish biochemical signaling pathways prior to entering human trials. Directly relevant to PENTACON, mice were used to predict and then assign mechanistic understanding to all recognized features ? thrombosis, hypertension, heart failure, dysrhythmia ? of the cardiovascular hazard in humans taking COX-2 selective NSAIDs (1,2). More than 20 genetic mouse models that disrupt or perturb the COX biosyntheticresponse pathway have been developed by PENTACON members, a unique resource for use in this proposal.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HL117798-01
Application #
8126768
Study Section
Special Emphasis Panel (ZGM1-PPBC-0 (GL))
Project Start
2012-08-01
Project End
2017-05-31
Budget Start
2012-08-01
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$311,358
Indirect Cost
$70,306
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Dong, Liang; Zou, Hechang; Yuan, Chong et al. (2016) Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis. J Biol Chem 291:4069-78
Bender, Gunes; Schexnaydre, Erin E; Murphy, Robert C et al. (2016) Membrane-dependent Activities of Human 15-LOX-2 and Its Murine Counterpart: IMPLICATIONS FOR MURINE MODELS OF ATHEROSCLEROSIS. J Biol Chem 291:19413-24
Zemski Berry, Karin A; Murphy, Robert C (2016) Phospholipid Ozonation Products Activate the 5-Lipoxygenase Pathway in Macrophages. Chem Res Toxicol 29:1355-64
Mazaleuskaya, Liudmila L; Lawson, John A; Li, Xuanwen et al. (2016) A broad-spectrum lipidomics screen of antiinflammatory drug combinations in human blood. JCI Insight 1:
Sahu, Ravi P; Harrison, Kathleen A; Weyerbacher, Jonathan et al. (2016) Radiation therapy generates platelet-activating factor agonists. Oncotarget 7:20788-800
Martin, Sarah A; Brash, Alan R; Murphy, Robert C (2016) The discovery and early structural studies of arachidonic acid. J Lipid Res 57:1126-32
FitzGerald, Garret A (2016) ImPRECISION: Limitations to Interpretation of a Large Randomized Clinical Trial. Circulation :
Guo, Lili; Worth, Andrew J; Mesaros, Clementina et al. (2016) Diisopropylethylamine/hexafluoroisopropanol-mediated ion-pairing ultra-high-performance liquid chromatography/mass spectrometry for phosphate and carboxylate metabolite analysis: utility for studying cellular metabolism. Rapid Commun Mass Spectrom 30:1835-45
Xiang, Yaozu; Hwa, John (2016) Regulation of VWF expression, and secretion in health and disease. Curr Opin Hematol 23:288-93
Dong, Liang; Zou, Hechang; Yuan, Chong et al. (2016) Interactions of 2-O-arachidonylglycerol ether and ibuprofen with the allosteric and catalytic subunits of human COX-2. J Lipid Res 57:1043-50

Showing the most recent 10 out of 56 publications