Cel 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. Dziedzina nauki natural sciencesbiological sciencesbiochemistrymedical and health sciencesclinical medicineangiologyvascular diseasesmedical and health scienceshealth sciencesinflammatory diseasesnatural scienceschemical sciencespolymer sciences Program(-y) 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) Temat(-y) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Zaproszenie do składania wniosków ERC-2012-StG_20111109 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca KAROLINSKA INSTITUTET Wkład UE € 1 252 980,00 Adres Nobels Vag 5 17177 Stockholm Szwecja Zobacz na mapie Region Östra Sverige Stockholm Stockholms län Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Therese Kindaker (Mrs.) Kierownik naukowy Hans Thomas Renné (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko KAROLINSKA INSTITUTET Szwecja Wkład UE € 1 252 980,00 Adres Nobels Vag 5 17177 Stockholm Zobacz na mapie Region Östra Sverige Stockholm Stockholms län Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Therese Kindaker (Mrs.) Kierownik naukowy Hans Thomas Renné (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Niemcy Wkład UE € 235 800,00 Adres Martinistrasse 52 20251 Hamburg Zobacz na mapie Region Hamburg Hamburg Hamburg Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Susanne Holzhüter (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych