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Shikonin attenuates sympathetic remodeling in chronic heart failure mice via regulating miR-124.

Authors
  • Liu, Wen-Lin1
  • Liu, Qiang2
  • 1 Affiliated Hospital of Guangdong Medical University; Clinical Research Center of Affiliated Hospital of Guangdong Medical University.
  • 2 Affiliated Hospital of Guangdong Medical University; Clinical Research Center of Affiliated Hospital of Guangdong Medical University. Electronic address: [email protected]
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Dec 03, 2019
Volume
520
Issue
2
Pages
359–365
Identifiers
DOI: 10.1016/j.bbrc.2019.10.038
PMID: 31604527
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Shikonin is a naphthoquinone compound extracted from the root of Lithospermum with various pharmacological activities. Sympathetic neural remodeling greatly contributes to chronic heart failure. Growing evidence has identified a critical role of microRNAs (miRNAs) in a variety of cardiac biological processes. This study aimed to verify whether shikonin could attenuate sympathetic neural remodeling and explore the possible regulatory role of miRNAs in this process. Shikonin was administered to mice after transverse aortic constriction (TAC). Immunohistochemistry and western blotting were used to assess the expression of TAC-induced sympathetic remodeling-related proteins. TAC-induced expression of the sympathetic remodeling-related proteins, tyrosine hydroxylase (TH), growth associated protein 43 (GAP43), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and nerve growth factor (NGF), was significantly decreased in cardiac tissues. MiR-124 expression significantly increased after heart failure and decreased after shikonin treatment. An adeno-associated virus 9 (AAV9) vector was packaged and used to transfect myocardial tissues of aortic-constricted mice with miR-124, resulting in increased heart miR-124 levels and inhibition of the effects of shikonin on sympathetic neural remodeling. Immunohistochemical staining showed that the density of TH-, GAP43-, and ChAT-positive nerves was significantly increased in aortic-constricted mice after transfection with AAV9-miR-124. Our data demonstrate that shikonin administration prevents sympathetic neural remodeling in mice with TAC-induced heart failure. The effects of shikonin on heart failure may be partly due to miR-124-mediated attenuation of sympathetic remodeling. Our results reveal a novel mechanism underlying the therapeutic effect of shikonin in heart failure. Copyright © 2019 Elsevier Inc. All rights reserved.

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