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
- Binder, C.J., et al., Innate and acquired immunity in atherogenesis. Nat Med, 2002. 8(11): p. 1218-26.
- Lusis, A.J., Atherosclerosis. Nature, 2000. 407(6801): p. 233-41.
- Piro, S., et al., Direct apoptotic effects of free fatty acids on human endothelial cells. Nutr Metab Cardiovasc Dis, 2008. 18(2): p. 96-104.
- Kiffin, R., U. Bandyopadhyay, and A.M. Cuervo, Oxidative stress and autophagy. Antioxid Redox Signal, 2006. 8(1-2): p. 152-62.
- Mallika, V., B. Goswami, and M. Rajappa, Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology, 2007. 58(5): p. 513-22.
- Boos, C.J., A.D. Blann, and G.Y. Lip, Assessment of endothelial damage/dysfunction: a focus on circulating endothelial cells. Methods Mol Med, 2007. 139: p. 211-24.
- Mizushima, N., Autophagy: process and function. Genes Dev, 2007. 21(22): p. 2861-73.
- Mizushima, N. and M. Komatsu, Autophagy: renovation of cells and tissues. Cell, 2011. 147(4): p. 728-41.
- Jung, C.H., et al., mTOR regulation of autophagy. FEBS Lett, 2010. 584(7): p. 1287-95.
- Noda, N.N. and F. Inagaki, Mechanisms of Autophagy. Annu Rev Biophys, 2015. 44: p. 101-22.
- Martinet, W., H. De Loof, and G.R. De Meyer, mTOR inhibition: a promising strategy for stabilization of atherosclerotic plaques. Atherosclerosis, 2014. 233(2): p. 601-7.
- Perrotta, I., The use of electron microscopy for the detection of autophagy in human atherosclerosis. Micron, 2013. 50: p. 7-13.
- Ouimet, M. and Y.L. Marcel, Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arterioscler Thromb Vasc Biol, 2012. 32(3): p. 575-81.
- Livak, K.J. and T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001. 25(4): p. 402-8.
- Cuervo, A.M., Autophagy: in sickness and in health. Trends Cell Biol, 2004. 14(2): p. 70-7.
- Shao, B.Z., et al., The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin, 2016. 37(2): p. 150-6.
- Wesselborg, S. and B. Stork, Autophagy signal transduction by ATG proteins: from hierarchies to networks. Cell Mol Life Sci, 2015. 72(24): p. 4721-57.
- Verheye, S., et al., Selective clearance of macrophages in atherosclerotic plaques by autophagy. J Am Coll Cardiol, 2007. 49(6): p. 706-15.
- Martinet, W. and G.R. De Meyer, Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential. Circ Res, 2009. 104(3): p. 304-17.
- De Meyer, G.R.Y., et al., Autophagy in Vascular Disease. Circulation Research, 2015. 116(3): p. 468-479.
- Li, W., et al., Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis. J Cell Mol Med, 2016.
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