Obiettivo Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. This system starts a cascade of procoagulant and proinflammatory reactions via the intrinsic pathway of coagulation, and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge.We have previously demonstrated that FXII is essential for thrombus formation while being dispensable for hemostatic processes that terminate blood loss. Challenging the dogma of a coagulation balance, targeting factor XII protected from cerebral ischemia without interfering with hemostasis. In contrast, excess FXII activity is associated with a life threatening inflammatory disorder, Hereditary angioedema. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema.The current investigations will explore roles of the FXII-driven contact system at the intersection of procoagulant and proinflammatory pathways using genetically altered murine models. We aim to understand activation, regulation and functions of the system for ischemic heart disease, vascular leakage in Hereditary angioedema, allergic airway inflammation as well as procoagulant reactions driven by bacterial infections in skin and lung.A key aspect of this proposal will be analysis of common principles, interactions and cross-talk between coagulation and inflammation, to identify novel therapeutic targets. Elucidating the FXII-driven contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory diseases. Campo scientifico natural sciencesbiological sciencesbiochemistrymedical and health sciencesclinical medicineangiologyvascular diseasesmedical and health scienceshealth sciencesinflammatory diseasesnatural scienceschemical sciencespolymer sciences Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2012-StG_20111109 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante KAROLINSKA INSTITUTET Contributo UE € 1 252 980,00 Indirizzo Nobels Vag 5 17177 Stockholm Svezia Mostra sulla mappa Regione Östra Sverige Stockholm Stockholms län Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Therese Kindaker (Mrs.) Ricercatore principale Hans Thomas Renné (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KAROLINSKA INSTITUTET Svezia Contributo UE € 1 252 980,00 Indirizzo Nobels Vag 5 17177 Stockholm Mostra sulla mappa Regione Östra Sverige Stockholm Stockholms län Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Therese Kindaker (Mrs.) Ricercatore principale Hans Thomas Renné (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Germania Contributo UE € 235 800,00 Indirizzo Martinistrasse 52 20251 Hamburg Mostra sulla mappa Regione Hamburg Hamburg Hamburg Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Susanne Holzhüter (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
