%0 Journal Article
%T Rock1 Inhibitor Abrogates Chronic Rejection in Rat Cardiac Model System
%A Li Zhang
%A Malgorzata Kloc
%A Neelam Tejpal
%A Junping You
%A Andrea M. Cordero-Reyes
%A Keith A. Youker
%A Rafik M. Ghobrial
%J Open Journal of Organ Transplant Surgery
%P 46-51
%@ 2163-9493
%D 2012
%I Scientific Research Publishing
%R 10.4236/ojots.2012.24012
%X <b>Background: </b>We have shown previously that the abrogation of acute and chronic rejection of rat cardiac allografts occurs through the down-regulation of RhoA pathway and involves the changes in RhoA kinase (ROCK)-dependent actin cytoskeleton and T cell motility. Here we studied the ability of the Y-27632, a highly selective inhibitor of Rho-associated protein kinase p160ROCK (ROCK1), to abrogate chronic rejection of the allograft and influence T cell infiltration. <b>Methods:</b> Heterotopic cardiac transplants were performed between donor Wistar Furth (WF) and ACI recipient rats. Controls received sub-therapeutic dose of cyclosporine (CsA, 10 mg/kg) for 3 days or 7 days therapeutic dose of cyclosporine. The experimental groups of ACI recipient received one preoperative dose of the Y-27632 inhibitor (2 mg/kg, gavage feed) in conjunction with the sub-therapeutic dose of CsA for 3 days or inhibitor alone for 7 days. The cardiac grafts were harvested at 100 days of post-transplantation for histological and immunohistochemical assessment of chronic rejection, vascular sclerosis, and infiltration by different T cell subtypes. <b>Results:</b> Cardiac allografts from recipients exposed to Y-27632 inhibitor in conjunction with sub-therapeutic dose of CsA showed drastically reduced vascular sclerosis, minimal myocardial total cellular infiltration, and were selectively infiltrated with Foxp3<sup>+</sup> T regulatory (Treg) cells. <b>Conclusions: </b>Our novel finding that a single dose of the ROCK1 inhibitor Y-27632 attenuates chronic rejection in rat cardiac model system by promoting development of Treg cells warrants its potential as a novel therapeutic agent specific for the inhibition of chronic rejection.
%K Chronic Rejection
%K Transplantation
%K ROCK1
%K RhoA
%K T Cell
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=24312