Objetivo 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. Ámbito científico natural sciencesbiological sciencesbiochemistrymedical and health sciencesclinical medicineangiologyvascular diseasesmedical and health scienceshealth sciencesinflammatory diseasesnatural scienceschemical sciencespolymer sciences Programa(s) 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) Tema(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Convocatoria de propuestas ERC-2012-StG_20111109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida KAROLINSKA INSTITUTET Aportación de la UE € 1 252 980,00 Dirección Nobels Vag 5 17177 Stockholm Suecia Ver en el mapa Región Östra Sverige Stockholm Stockholms län Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Therese Kindaker (Mrs.) Investigador principal Hans Thomas Renné (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo KAROLINSKA INSTITUTET Suecia Aportación de la UE € 1 252 980,00 Dirección Nobels Vag 5 17177 Stockholm Ver en el mapa Región Östra Sverige Stockholm Stockholms län Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Therese Kindaker (Mrs.) Investigador principal Hans Thomas Renné (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Alemania Aportación de la UE € 235 800,00 Dirección Martinistrasse 52 20251 Hamburg Ver en el mapa Región Hamburg Hamburg Hamburg Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Susanne Holzhüter (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos