Celastrol ameliorates vascular neointimal hyperplasia through Wnt5a-involved autophagy.

Abstract

Neointimal hyperplasia caused by the excessive proliferation of vascular smooth muscle cells (VSMCs) is the pathological basis of restenosis. However, there are few effective strategies to prevent restenosis. Celastrol, a pentacyclic triterpene, has been recently documented to be beneficial to certain cardiovascular diseases. Based on its significant effect on autophagy, we proposed that celastrol could attenuate restenosis through enhancing autophagy of VSMCs. In the present study, we found that celastrol effectively inhibited the intimal hyperplasia and hyperproliferation of VSMCs by inducing autophagy. It was revealed that autophagy promoted by celastrol could induce the lysosomal degradation of c-MYC, which might be a possible mechanism contributing to the reduction of VSMCs proliferation. The Wnt5a/PKC/mTOR signaling pathway was found to be an underlying mechanism for celastrol to induce autophagy and inhibit the VSMCs proliferation. These observations indicate that celastrol may be a novel drug with a great potential to prevent restenosis.

• Authors: Ya-Ning Shi, Le-Ping Liu, Chang-Feng Deng, Tan-Jun Zhao, Zhe Shi, Jian-Ye Yan, Yong-Zhen Gong, Duan-Fang Liao, Li Qin
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 17 Issue 10 Pg. 2561-2575 ( 2021) ISSN: 1449-2288 [Electronic] Australia
• PMID: 34326694 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Pentacyclic Triterpenes
• Wnt-5a Protein
• TOR Serine-Threonine Kinases
• celastrol

Topics

• Animals
• Autophagy (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Femoral Artery (injuries)
• Humans
• Hyperplasia (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Myocytes, Smooth Muscle (cytology, drug effects, metabolism)
• Neointima
• Pentacyclic Triterpenes (pharmacology)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Wnt-5a Protein (metabolism)
• Wound Healing (drug effects)