Abstract 334: Circadian Clock Influences in Atherosclerosis Are Revealed Using a Transplant Model of Accelerated Atherogenesis
The circadian clock within blood vessels is an important influence in flow induced vascular remodeling and transplant arteriosclerosis. Much less is known regarding the role of the circadian clock in high cholesterol induced-atherosclerosis. To assess atherogenesis, we implemented a novel transplant model approach, previously tested in wild-type and circadian clock mutant recipient mice, but herein using recipient mice that were hypercholesterolemic_the apoE knockout mice. Using these recipient mice, syngeneic heterotopic transplantation of segments of thoracic aortas (all were lesion free in naïve conditions) from donor mice that were wild-type, mutated in the Bmal1 (Bmal1-KO) gene, or mutated in the apoE gene (apoE-KO) were grafted into the neck circulation (common carotid artery) of the apoE knockout mice. After 4 weeks of transplantation, a significant lipid rich lesion that stained positive with oil red-o was observed in the Bmal1-KO grafts that were placed in apoE knockout mice, while naïve Bmal1-KO aorta exhibited no oil-red positive lesion. Suprisingly, there were no substantial lesion in WT or apoE-KO aortic grafts placed in the apoE-KO recipient mice. These data suggest that the circadian clock may influence the progression of atherosclerosis.
- © 2012 by American Heart Association, Inc.