Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes in apolipoprotein E knockout mice.

Background: Acute myocardial infarction and stroke occur more frequently in the morning, suggesting a role of the circadian clock in these main causes of death, secondary to atherosclerosis.

Objectives: To investigate the expression of clock genes, apoptosis-related genes and atherosclerosis-related genes in the process of atherosclerosis.

Methods: Apolipoprotein E knockout (ApoE-/-) mice were used to establish animal models of early and advanced atherosclerosis. Real-time polymerase chain reaction, Western blotting and microarray assays were used to detect the expression of clock genes, apoptosis-related genes and atherosclerosis-related genes.

Results: Clock genes in ApoE-/- and C57BL/6J mouse hearts exhibited daily oscillations at the messenger RNA level. However, the expression level and rhythm between ApoE-/- and C57BL/6J mice were significantly different. Moreover, the changes became more significant as atherosclerosis developed. c-Myc and p53 genes exhibited circadian expression in C57BL/6J mice at messenger RNA and protein levels. However, the rhythm in ApoE-/- mice disappeared completely. Bcl-2 and Bax did not show daily rhythm in either strain of mouse. Aside from apoptosis-related genes, several atherosclerosis-related genes expressed time-dependent behaviour in C57BL/6J mice but not in ApoE-/- mice.

Conclusions: Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes may play important roles in atherosclerosis and its complications.