The suprachiasmatic nucleus of the brain is the circadian center, relaying 
rhythmic environmental and behavioral information to peripheral tissues to 
control circadian physiology. As such, central clock dysfunction can alter 
systemic homeostasis to consequently impair peripheral physiology in a manner 
that is secondary to circadian malfunction. To determine the impact of circadian 
clock function in organ transplantation and dissect the influence of intrinsic 
tissue clocks versus extrinsic clocks, we implemented a blood vessel grafting 
approach to surgically assemble a chimeric mouse that was part wild-type (WT) 
and part circadian clock mutant. Arterial isografts from donor WT mice that had 
been anastamosed to common carotid arteries of recipient WT mice (WT:WT) 
exhibited no pathology in this syngeneic transplant strategy. Similarly, when WT 
grafts were anastamosed to mice with disrupted circadian clocks, the structural 
features of the WT grafts immersed in the milieu of circadian malfunction were 
normal and absent of lesions, comparable to WT:WT grafts. In contrast, aortic 
grafts from Bmal1 knockout (KO) or Period-2,3 double-KO mice transplanted into 
littermate control WT mice developed robust arteriosclerotic disease. These 
lesions observed in donor grafts of Bmal1-KO were associated with up-regulation 
in T-cell receptors, macrophages, and infiltrating cells in the vascular grafts, 
but were independent of hemodynamics and B and T cell-mediated immunity. These 
data demonstrate the significance of intrinsic tissue clocks as an autonomous 
influence in experimental models of arteriosclerotic disease, which may have 
implications with regard to the influence of circadian clock function in organ 
transplantation.