Effect of hyperlipidemia on the expression of circadian genes in apolipoprotein E knock-out atherosclerotic mice

Abstract

BackgroundCircadian patterns of cardiovascular vulnerability were well characterized, with a peak incidence of acute myocardial infarction and stroke secondary to atherosclerosis in the morning, which showed the circadian clock may take part in the pathological process of atherosclerosis induced by hyperlipidemia. Hence, the effect of hyperlipidemia on the expression of circadian genes was investigated in atherosclerotic mouse model.ResultsIn apoE-/-mice on regular chow or high-fat diet, an atherosclerotic mouse model induced by heperlipidemia, we found that the peak concentration of serum lipids was showed four or eight hours later in apoE-/- mice, compared to C57BL/6J mice. During the artificial light period, a reduce in circulating level of serum lipids corresponded with the observed increase of the expression levels of some the transcription factors involved in lipid metabolism, such as PPARα and RXRα. Meanwhile, the expression of circadian genes was changed following with amplitude reduced or the peak mRNA level delayed.ConclusionsOur studies indicated that heperlipidemia altered both the rhythmicity and expression of circadian genes. Diet-induced circadian disruption may affect the process of atherosclerosis and some acute cardiovascular disease.

Degeneration and energy shortage in the suprachiasmatic nucleus underlies the circadian rhythm disturbance in ApoE−/− mice: implications for Alzheimer’s disease

“…Metabolic disorders including dyslipidaemia and diabetes are epidemiologically linked to AD38. High-fat diets are known to alter both the central and peripheral clocks, including the locomotor activity1139. Hypothetically, the elevated cholesterol levels in ApoE −/− mice could reset the SCN central clock.…”

“…The clock and atherosclerosis-related genes were found differentially expressed in ApoE −/− mice. For example, ApoE −/− mice showed phase delay in the circadian pattern of serum lipid levels11, altered expression of clock12 and atherosclerosis/thrombosis-related genes13.…”

Intracellular high cholesterol content disorders the clock genes, apoptosis-related genes and fibrinolytic-related genes rhythmic expressions in human plaque-derived vascular smooth muscle cells

“…So circadian rhythm disorder of these CCGs in PVSMCs should be attributed to the attenuation expression of clock genes we reported previously. Previous studies have confirmed that the hyperlipidaemia could impair the circadian clock in vivo and in vitro [6, 26]. Especially Chen S et al [6] showed that the free fatty acids (FFAs) could inhibit the clock genes expressions in contractile VSMCs via the suppression of Smarcd1.…”

Hyperlipidaemia impairs the circadian clock and physiological homeostasis of vascular smooth muscle cells via the suppression of Smarcd1

“…Peripheral circadian clock profiles have been increasingly recognized as important players in tissue physiology. Recent studies have indicated that hyperlipidaemia reduces amplitudes and perturbs the periodicity of clock genes in cardiovascular and hepatic tissues in apoE ‐deficient mice . In humans, SNPs in the Per2 locus functionally intersected with total fasting saturated fatty acid levels to modulate circulating apoC‐II and apoB‐48, which is relevant to the dyslipidaemia of metabolic syndromes .…”