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

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

  • Front Pharmacol. 2021 Jun 25;12:673366. doi: 10.3389/fphar.2021.673366.
Yifei Chen 1 2 Fangpu Yu 1 Yu Zhang 1 Mengmeng Li 1 Mingxue Di 1 Weijia Chen 1 Xiaolin Liu 1 Yun Zhang 1 Mei Zhang 1
Affiliations

Affiliations

  • 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Department of Echocardiography, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
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.

Keywords

atherosclerosis; autophagy; lipid metabolism; macrophages; tongxinluo.

Figures
Products