Fifty percent of transplant recipients develop accelerated atherosclerosis in their grafts. This accelerated form of atherosclerosis is the most important limitation to long-term survival. An important and common problem in solid organ transplantation is the consequences and contributions of hyperglycemia and hypertriglyceridemia towards vascular disease.
Our specific aims are to compare two new models of TxCAD with type 1 and type 2 diabetes to a standard model (Fisher/Lewis), as well as optimize these new models by characterizing their reproducibility of phenotype, time course, morphological and cellular features. We will identify similarities and delineate differences in TxCAD morphology between our models and a standard heterotopic model in rodents (i.e. Lewis/Fisher); define the time course of TxCAD lesions; define the spatial characteristics (i.e., involvement of vessels at the base, mid -ventricle and apex) determine the reproducibility of the new models; and determine the phenotypes of the cellular composition of the lesions.
As a service research contract company, we will provide two well phenotype new models for study of accelerated atherosclerosis that are reflective of the human conditions. Also, we will contract to test novel therapies for transplant associated accelerated atherosclerosis.
| Cantin, Bernard; Zhu, Dening; Wen, Peizhong et al. (2002) Preferential involvement of larger vessels in a rat model of diabetes-induced graft vasculopathy. J Heart Lung Transplant 21:1040-3 |
| Cantin, Bernard; Zhu, Dening; Wen, Peizhong et al. (2002) Reversal of diabetes-induced rat graft transplant coronary artery disease by metformin. J Heart Lung Transplant 21:637-43 |
| Cantin, B; Wen, P; Zhu, D et al. (2001) Transplant coronary artery disease: a novel model independent of cellular alloimmune response. Circulation 104:2615-9 |
