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

Effect of hyperlipidemia on the expression of circadian genes in apolipoprotein E knock-out atherosclerotic mice.
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DOI:
10.1186/1476-511x-8-60
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发表时间:
2009-12-30
影响因子:
4.5
通讯作者:
Qian R
Qian R
中科院分区:
医学3区
文献类型:
--
作者:
Hou L;Lu C;Huang Y;Chen S;Hua L;Qian R

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心血管易损性的昼夜节律特征较好,急性心肌梗死和继发于动脉粥样硬化的卒中高发于早晨,提示昼夜节律可能参与了高脂血症致动脉粥样硬化的病理过程。因此,我们研究了高脂血症对动脉粥样硬化小鼠昼夜节律基因表达的影响。在普通饲料或高脂饮食的apoE-/-小鼠中,我们发现与C57BL/6J小鼠相比,apoE-/-小鼠的血脂峰值出现的时间比C57BL/6J小鼠晚4或8小时。在人工光照期间,循环中血脂水平的降低与参与脂代谢的一些转录因子如PPARα和RXRα的表达水平升高相对应。同时,昼夜节律基因的表达随着振幅的降低或峰值水平的延迟而改变。我们的研究表明,高脂血症改变了昼夜节律基因的节律性和表达。饮食诱导的昼夜节律紊乱可能会影响动脉粥样硬化和一些急性心血管疾病的进程。
Circadian 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. In 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. Our 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.