Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss.
