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10.1073/pnas.1718600115 http://scihub22266oqcxt.onion/10.1073/pnas.1718600115 C5798377!5798377 !29343648     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29343648 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Proc+Natl+Acad+Sci+U+S+A 2018 ; 115 (5 ): E982-E991 Nephropedia Template TP {{tp|p=29343648 |t=2018. PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury |pdf=|usr=}}{{29343648 }} gab.com Text PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29343648 #FOAvip 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 through G??, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-?B-mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling. Twit Text FOAVip PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29343648 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29343648 #FOAvip English Wikipedia <ref>{{Cite pmid|29343648 }}</ref> PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury #MMPMID29343648 De Ceunynck K ; Peters CG ; Jain A ; Higgins SJ ; Aisiku O ; Fitch-Tewfik JL ; Chaudhry SA ; Dockendorff C ; Parikh SM ; Ingber DE ; Flaumenhaft R Proc Natl Acad Sci U S A 2018[Jan]; 115 (5 ): E982-E991 PMID29343648 show ga 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 through G??, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-?B-mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling. |Animals [MESH] |Apoptosis [MESH] |Endothelial Cells/*metabolism [MESH] |Factor Xa/metabolism [MESH] |Gene Knockdown Techniques [MESH] |Glycoproteins/genetics/metabolism [MESH] |Human Umbilical Vein Endothelial Cells [MESH] |Humans [MESH] |Inflammation/*metabolism [MESH] |Lipopolysaccharides [MESH] |Male [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH] |Microcirculation [MESH] |Peptide Hydrolases/metabolism [MESH] |Receptor, PAR-1/*agonists [MESH] |Receptors, G-Protein-Coupled/metabolism [MESH] |Signal Transduction [MESH] |Thrombosis/*metabolism [MESH] |Transcription, Genetic [MESH]PAR1 agonists stimulate APC-like endothelial cytoprotection and confer(epmc).pdf DeepDyve Pubget Overpricing