Heart Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Heart Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

VEGFR-1 and -2 regulate inflammation, myocardial angiogenesis, and arteriosclerosis in chronically rejecting cardiac allografts.

Raisky O, Nykänen AI, Krebs R, Hollmén M, Keränen MA, Tikkanen JM, Sihvola R, Alhonen L, Salven P, Wu Y, Hicklin DJ, Alitalo K, Koskinen PK, Lemström KB

Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Finland.

OBJECTIVE: Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts. METHODS AND RESULTS: Chronic rejection in mouse cardiac allografts induced primitive myocardial, adventitial, and intimal angiogenesis with endothelial expression of CD31, stem cell marker c-kit, and VEGFR-2. Experiments using marker gene mice or rats as cardiac allograft recipients revealed that replacement of cardiac allograft endothelial cells with recipient bone marrow- or non-bone marrow-derived cells was rare and restricted only to sites with severe injury. Targeting VEGFR-1 with neutralizing antibodies in mice reduced allograft CD11b+ myelomonocyte infiltration and allograft arteriosclerosis. VEGFR-2 inhibition prevented myocardial c-kit+ and CD31+ angiogenesis in the allograft, and decreased allograft inflammation and arteriosclerosis. CONCLUSIONS: These results suggest interplay of inflammation, primitive donor-derived myocardial angiogenesis, and arteriosclerosis in transplanted hearts, and that targeting VEGFR-1 and -2 differentially regulate these pathological reparative processes.

Published 22 March 2007 in Arterioscler Thromb Vasc Biol, 27(4): 819-25.
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