Abstract

The aim of this project is to define mechanisms of thrombus formation through the study of platelet interactions with adhesive proteins - in particular, fibrinogen/fibrin, von Willebrand factor and collagen type I - under the influence of shear stress. A distinctive feature of this project is the development and use of experimental models, based on laser confocal microscopy and real-time epifluorescent microscopy, for the quantitative evaluation of thrombus formation under defined conditions of flow. The effect of shear forces on the formation of stable platelet thrombi is being evaluated under hemodynamic conditions that mimic those encountered in different districts of the arterial circulation, in order to define how distinct structures in the adhesive molecules under study, including previously unrecognized domains, mediate platelet deposition and accumulation at sites of vascular injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000833-25
Application #
6265224
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
25
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Winn, Virginia D; Gormley, Matthew; Fisher, Susan J (2011) The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface. Pregnancy Hypertens 1:100-8
Delaney, Joseph A C; Scherzer, Rebecca; Biggs, Mary L et al. (2010) Associations of antiretroviral drug use and HIV-specific risk factors with carotid intima-media thickness. AIDS 24:2201-9
Pan, Warren W; Li, Jain-Dong; Huang, Shuang et al. (2010) Synergistic activation of NF-{kappa}B by bacterial chemoattractant and TNF{alpha} is mediated by p38 MAPK-dependent RelA acetylation. J Biol Chem 285:34348-54
Huang, XueSong; Chen, Ling-Yu; Doerner, Astrid M et al. (2009) An atypical protein kinase C (PKC zeta) plays a critical role in lipopolysaccharide-activated NF-kappa B in human peripheral blood monocytes and macrophages. J Immunol 182:5810-5
Mukherjee, Sumanta; Chen, Ling-Yu; Papadimos, Thomas J et al. (2009) Lipopolysaccharide-driven Th2 cytokine production in macrophages is regulated by both MyD88 and TRAM. J Biol Chem 284:29391-8
Chen, Ling-Yu; Pan, Zhixing K (2009) Synergistic activation of leukocytes by bacterial chemoattractants: potential drug targets. Endocr Metab Immune Disord Drug Targets 9:361-70
Chen, Ling-Yu; Pan, Warren W; Chen, Miao et al. (2009) Synergistic induction of inflammation by bacterial products lipopolysaccharide and fMLP: an important microbial pathogenic mechanism. J Immunol 182:2518-24
Ito, Tatsuo; Yadav, Neelu; Lee, Jaeho et al. (2009) Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. BMC Dev Biol 9:47
Price, Richard W; Parham, Robin; Kroll, Jing Lu et al. (2008) Enfuvirtide cerebrospinal fluid (CSF) pharmacokinetics and potential use in defining CSF HIV-1 origin. Antivir Ther 13:369-74
Dawson, Arthur; Abel, Susan L; Loving, Richard T et al. (2008) CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic control during sleep. J Clin Sleep Med 4:538-42

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