Core A will continue to provide standardized procedures for the quantitative study of processes relevant to thrombus formation and regulation using In vivo models in the murine circulation and ex vivo models in perfusion chambers under the influence of defined flow forces. Core A will also perform isolation, culture and characterization of relevant vascular cells. Project 1 (Griffin;39% use) will utilize primarily in vivo models to study the antithrombotic properties of wild type and mutant activated protein C and protein S. Project 2 (Ginsberg;22% use) will utilize in vivo models to study the arterial thrombogenic phenotype resulting from functional alterations of CD98, as well as ex vivo models to study the thrombogenic potential of smooth muscle cells derived from the same mutant mice. Project 3 (Ruf;39% use) will utilize in vivo models of response to vascular injury to explore the mechanisms leading to the induction of tissue factor activity, as well as complementary ex vivo fiow models to explore the mechanisms of tissue factor decryption in relevant vascular cells under more constrained experimental conditions.

Public Health Relevance

Core A will ensure uniformity of methodological approach with respect to the use of key experimental models that will be crucial to validate the in vivo relevance of the results obtained by the individual projects.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01HL031950-29
Application #
8686044
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
29
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Langer, Florian; Ruf, Wolfram (2014) Synergies of phosphatidylserine and protein disulfide isomerase in tissue factor activation. Thromb Haemost 111:590-7
von Drygalski, Annette; Bhat, Vikas; Gale, Andrew J et al. (2014) An engineered factor Va prevents bleeding induced by anticoagulant wt activated protein C. PLoS One 9:e104304
Winkler, Ethan A; Sengillo, Jesse D; Sagare, Abhay P et al. (2014) Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci U S A 111:E1035-42
Mosnier, Laurent O; Zlokovic, Berislav V; Griffin, John H (2014) Cytoprotective-selective activated protein C therapy for ischaemic stroke. Thromb Haemost 112:883-92
von Drygalski, A; Cramer, T J; Bhat, V et al. (2014) Improved hemostasis in hemophilia mice by means of an engineered factor Va mutant. J Thromb Haemost 12:363-72
Li, A; Guo, Q; Kim, C et al. (2014) Integrin ?II b tail distal of GFFKR participates in inside-out ?II b ?3 activation. J Thromb Haemost 12:1145-55
von Drygalski, Annette; Furlan-Freguia, Christian; Ruf, Wolfram et al. (2013) Organ-specific protection against lipopolysaccharide-induced vascular leak is dependent on the endothelial protein C receptor. Arterioscler Thromb Vasc Biol 33:769-76
Wang, Yaoming; Sinha, Ranjeet Kumar; Mosnier, Laurent O et al. (2013) Neurotoxicity of the anticoagulant-selective E149A-activated protein C variant after focal ischemic stroke in mice. Blood Cells Mol Dis 51:104-8
Liu, Yani; Davidson, Brian P; Yue, Qi et al. (2013) Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis effects of antioxidant therapy with NADPH oxidase inhibition. Circ Cardiovasc Imaging 6:74-82
Burnier, Laurent; Fernandez, Jose A; Griffin, John H (2013) Antibody SPC-54 provides acute in vivo blockage of the murine protein C system. Blood Cells Mol Dis 50:252-8

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