The Changing Regulation of Autophagy in Atherosclerosis in ApoE Gene Knockout Mice

Author(s): Wang Hongliang, Xudong PAN, Aijun MA, Shaonan YANG, Juanjuan MA, Zhaozhi ZHANG, Ting LI, Mei WU

Aim To investage the changes of autophagy in different stages of atherosclerosis (AS) in Apolipoprotein E gene knockout (ApoE-/-) mice. Methods 6-weeks-old male ApoE-/- mice (No.=40) were randomly divided into two groups and fed with common adaptability diet for 2 weeks. The mice of the control group (No.=10) received a sham operation and the common diet for another 8 weeks. While the model mice (No.=30) received a right common carotid artery cannulation and randomly subdivided into three groups (the 2 weeks, the 4 weeks and the 8 weeks) and fed with the high fat diet separately for 2 weeks, 4 weeks and 8 weeks. The blood samples obtained from femoral arteries were studied via the biochemical analysis. The right common carotid arteries were split out for histopathological study. Real-time quantitative polymerase chain reaction (qRT-PCR) and the western blot were used to detect the relative expression levels of mRNA and protein about mTOR. Results As the operation time prolonged the lipid levels especially TG and LDL_c were time relative increased. The histopathological analysis results showed that there was a small amount of cells infiltrated in the common carotid artery in the 2 weeks, although the wall was still unspoiled. The vascular wall in the 4 weeks was messy and there was thrombus in the vascular lumen. The thickness of the right common carotid artery in the 8 weeks was higher than others and its elastic membranes significantly decreased. The qRT-PCR and western blot detection suggested the mRNA and protein expression of mTOR in the 4 weeks was higher than the 2 weeks and the 8 weeks, and the expression in the 8 weeks was also higher than those in the 2 weeks. Conclusions Autophagy was continuously stimulated during AS formation,however, the levels of autophagy will decrease after reaching the peak at a time.

Autophagy, mTOR, Atherosclerosis, ApoE-/- mice

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