01948nas a2200121   4500008004100000245010600041210006900147260001200216300001400228490000700242520151100249856006601760       2015                        eng d00aIschemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts0 aIschemiaReperfusion Injury Enhances Lymphatic Endothelial VEGFR3  c12/2015  a1160-11720 v163 aOrgan damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia–reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lymphangiogenic VEGF-C/VEGFR3 pathway during cardiac allograft IRI regulates organ damage and subsequent interplay between innate and adaptive immunity. We found that cardiac allograft IRI, within hours, increased graft VEGF-C expression and lymphatic vessel activation in the form of increased lymphatic VEGFR3 and adhesion protein expression. Pharmacological VEGF-C/VEGFR3 stimulation resulted in early lymphatic activation and later increase in allograft inflammation. In contrast, pharmacological VEGF-C/VEGFR3 inhibition during cardiac allograft IRI decreased early lymphatic vessel activation with subsequent dampening of acute and chronic rejection. Genetic deletion of VEGFR3 specifically in the lymphatics of the transplanted heart recapitulated the survival effect achieved by pharmacological VEGF-C/VEGFR3 inhibition. Our results suggest that tissue damage rapidly changes lymphatic vessel phenotype, which, in turn, may shape the interplay of innate and adaptive immunity. Importantly, VEGF-C/VEGFR3 inhibition during solid organ transplant IRI could be used as lymphatic-targeted immunomodulatory therapy to prevent acute and chronic rejection.  uhttp://onlinelibrary.wiley.com/doi/10.1111/ajt.13564/abstract00594nas a2200181   4500008004100000245008300041210006900124260003800193100001600231700001700247700001600264700001700280700001700297700001400314700001600328700001600344856005200360       2001                        eng d00aSignalling via VEGFR-3 is sufficient for lymphangiogenesis in transgenic mice.0 aSignalling via VEGFR3 is sufficient for lymphangiogenesis in tra  aMiami Beach, Floridac2001/10/29/1 aJussila, L.1 aVeikkola, T.1 aJeltsch, M.1 aThurston, G.1 aMcDonald, D.1 aAchen, M.1 aStacker, S.1 aAlitalo, K.  uhttps://www.jeltsch.org/Jussila2001?language=hu