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Full-Text Articles in Chemistry
Par1 Agonists Stimulate Apc-Like Endothelial Cytoprotection And Confer Resistance To Thromboinflammatory Injury, Karen De Ceunynck, Christian G. Peters, Abhishek Jain, Sarah J. Higgins, Omozuanvbo Aisiku, Jennifer L. Fitch-Tewfik, Sharjeel A. Chaudhry, Chris Dockendorff, Samir M. Parikh, Donald E. Ingber, Robert Flaumenhaft
Par1 Agonists Stimulate Apc-Like Endothelial Cytoprotection And Confer Resistance To Thromboinflammatory Injury, Karen De Ceunynck, Christian G. Peters, Abhishek Jain, Sarah J. Higgins, Omozuanvbo Aisiku, Jennifer L. Fitch-Tewfik, Sharjeel A. Chaudhry, Chris Dockendorff, Samir M. Parikh, Donald E. Ingber, Robert Flaumenhaft
Chemistry Faculty Research and Publications
Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed “parmodulins” that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling …