Protective genes in the vessel wall: Modulators of graft survival and function

Protecting a vascularized graft from transplant arteriosclerosis requires inhibition of host immune effectors, but protective responses emanating from the graft aimed at maintaining/restoring "homeostasis" might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), Bcl-xL, inducible nitric oxide synthase (iNOS), and others in the vessel wall of rodent allografts and xenografts correlates with absence of transplant arteriosclerosis. Given the antiapoptotic and anti-inflammatory functions of these genes in endothelial cells and their anti-inflammatory/antiproliferative and sometimes proapoptotic function in neointimal smooth muscle cells, we hypothesize that their expression survives to limit graft injury by maintaining vascular integrity, controlling inflammation and promoting healing. Beyond this beneficial effect, their expression in the vessel wall may also positively impact the alloimmune response.