Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 501, Issue 2, Pages 336-342Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.03.094
Keywords
Tongxinluo; Macrophage; Apoptosis; Autophagy; Atherosclerosis
Categories
Funding
- National Research Program of China [2016YFC1300302]
- National Natural Science Foundation of China [81470559, 81770439, 81700387]
- International Collaboration and Exchange Program of China [81320108004]
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In advanced atherosclerosis, a large number of necrotic core increases plaque vulnerability, which leads to the occurrence of acute atherothrombotic cardiovascular events. Macrophage apoptosis plays an important role in secondary necrosis. The present study aimed to examine and describe the effect of the traditional Chinese medication Tongxinluo (TXL) on macrophage apoptosis in advanced atherosclerotic plaques and to explore its mechanism. By observing the effect of TXL on ox-LDL-stimulated macrophage apoptosis, it was shown that TXL significantly inhibited ox-LDL-induced apoptosis of macrophages by enhancing autophagy. Therapeutic mechanism of TXL included increasing the expression of Beclin-1 and improving the dissociation of Bcl-2-Beclin-1 Complex. Apolipoprotein E knockout (apoE-/-) mice with a high fat diet were divided into four groups: saline group (Saline gavage), low dose TXL group (0.38 g/kg/d, gavage), medium dose TXL group (0.75 g/kg/day, gavage), and high dose TXL group (1.5 g/kg/day, gavage). 4 weeks after carotid-artery surgery, lentiviral of Beclin-1 silencing was injected through the tail vein. TXL treatment significantly reduced macrophage apoptosis dose-dependently and the result was blocked by Beclin-1 silencing. In addition, the increased Lc3b dots by TXL almost localized to macrophages in advanced atherosclerotic plaque. Compared with the same dose of TXL shBeclin-1 group, plaque area and vulnerability index of TXL groups decreased. The anti-apoptosis effects of TXL on atherosclerosis was related to the improvement of autophagy via Beclin-1. (C) 2018 The Authors. Published by Elsevier Inc.
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