Fiche du document
2012
- doi: 10.1016/j.humimm.2012.07.334
- issn: 0198-8859
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.humimm.2012.07.334
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/22863981
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1879-1166
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_39F41380CB893
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Survival skills Survival after airplane accidents, shipwrecks, etc White cells White blood cells Leukocytes Inflammatory process Pattern Model Blood--Flow Agency (Philosophy) Agents Person (Philosophy)Citer ce document
O. Dormond et al., « Targeting the intragraft microenvironment and the development of chronic allograft rejection. », Serveur académique Lausannois, ID : 10.1016/j.humimm.2012.07.334
Métriques
Partage / Export
Résumé
In this review, we discuss a paradigm whereby changes in the intragraft microenvironment promote or sustain the development of chronic allograft rejection. A key feature of this model involves the microvasculature including (a) endothelial cell (EC) destruction, and (b) EC proliferation, both of which result from alloimmune leukocyte- and/or alloantibody-induced responses. These changes in the microvasculature likely create abnormal blood flow patterns and thus promote local tissue hypoxia. Another feature of the chronic rejection microenvironment involves the overexpression of vascular endothelial growth factor (VEGF). VEGF stimulates EC activation and proliferation and it has potential to sustain inflammation via direct interactions with leukocytes. In this manner, VEGF may promote ongoing tissue injury. Finally, we review how these events can be targeted therapeutically using mTOR inhibitors. EC activation and proliferation as well as VEGF-VEGFR interactions require PI-3K/Akt/mTOR intracellular signaling. Thus, agents that inhibit this signaling pathway within the graft may also target the progression of chronic rejection and thus promote long-term graft survival.