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Telmisartan-induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy

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Abstract

Foam cell formation is the hallmark of atherosclerosis. Both telmisartan and autophagy protect against the development of atherosclerosis. However, it has yet to be elucidated whether telmisartan prevents vascular smooth muscle cell (VSMC)-derived foam cell formation. Vascular smooth muscle cells isolated from the thoracic aorta of male C57BL/6J mice were used for this study. To induce foam cell formation, primary VSMCs were incubated in 80 μg/ml oxLDL for 24 h. LC3, beclin-1, PPARγ, AMPK, p-AMPK, mTOR and p-mTOR expression were determined via Western blot. Lipid accumulation was evaluated via oil red O staining and intracellular total cholesterol level measurement. Our study demonstrated that telmisartan dose-dependently increased the expression of beclin-1, the LC3II/LC3I ratio and the quantity of GFP-labeled autophagosomes, displaying a peak effect at 10 μM. In control siRNA-transfected VSMCs, telmisartan (10 μM) decreased lipid droplet accumulation and the total cholesterol level significantly. In contrast, in Atg7 siRNA-transfected VSMCs, telmisartan failed to attenuate lipid accumulation. In addition, telmisartan dose-dependently increased the expression of PPARγ and p-AMPK and decreased the expression of p-mTOR. GW9662 attenuated the telmisartan-induced increase in PPARγ expression, the LC3-II/LC3-I ratio and p-AMPK expression and the telmisartan-induced decrease in p-mTOR expression. Compound C restored mTOR activity and abolished the increase in the LC3-II/LC3-I ratio. Rapamycin significantly reduced p-mTOR expression and increased the LC3-II/LC3-I ratio. In conclusion, this study provides evidence that the chronic pharmacological activation of the PPARγ-mediated autophagy pathway using telmisartan may represent a promising therapeutic strategy for atherosclerosis.

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Acknowledgments

This study was supported by the Natural Science Foundation Project of CQ CSTC (No. CSTC2012JJJQ10003) and the National Natural Science Foundation of China (No. 81271282; No. 81400967; No. 81471193).

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Authors and Affiliations

  1. Department of Neurology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People’s Republic of China

    Bing-Hu Li, Shao-Qiong Liao, Yan-Wei Yin, Chun-Yan Long, Lu Guo, Xiao-Jie Cao, Yun Liu, Yi Zhou, Chang-Yue Gao, Li-Li Zhang & Jing-Cheng Li

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  1. Bing-Hu Li
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Correspondence to Li-Li Zhang or Jing-Cheng Li.

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Li, BH., Liao, SQ., Yin, YW. et al. Telmisartan-induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy. Mol Biol Rep 42, 179–186 (2015). https://doi.org/10.1007/s11033-014-3757-6

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  • DOI: https://doi.org/10.1007/s11033-014-3757-6

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