Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy.

Yifei Chen,Xiaolin Liu,Yu Zhang,Yun Zhang,Weijia Chen,Fangpu Yu,Mingxue Di,Mei Zhang,Mengmeng Li

doi:10.3389/fphar.2021.673366

Abstract

Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages in vitro by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis in vivo. Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages in vitro. Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. In vitro TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL (p < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1.

Highlights

Atherosclerosis is a chronic inflammatory disease caused because of lipid dysfunction that occurs in the walls of the large and middle arterial blood vessels (Lusis, 2000)
In connection with the earlier research findings (Chen et al, 2018), these data indicate that TXL improves lipid deposition in advanced atherosclerotic plaques, and this effect is induced by autophagy
We investigated how TXL affects lipid deposition in advanced atherosclerotic plaques and lipid metabolism in macrophages

Summary

Introduction

Atherosclerosis is a chronic inflammatory disease caused because of lipid dysfunction that occurs in the walls of the large and middle arterial blood vessels (Lusis, 2000). In the initial stages of atherosclerosis, endothelial function is disturbed and apolipoprotein B lipoproteins, such as lowdensity lipoprotein (LDL), are retained in the subendothelium, while the endothelium is activated to secrete chemokines and monocyte adhesion molecules. Tongxinluo Attenuates Lipidosis by Autophagy endothelium, they differentiate into macrophages, which take up the subcutaneous lipoproteins. The formation of foam cells can promote the development of atherosclerosis (Mannarino and Pirro, 2008; Libby et al, 2011; Moore et al, 2013). The reduction in the conversion of macrophages to foam cells will be an effective therapeutic strategy for reversing plaque lipid accumulation

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