PMID- 31604527
OWN - NLM
STAT- MEDLINE
DCOM- 20200720
LR  - 20220622
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 520
IP  - 2
DP  - 2019 Dec 3
TI  - Shikonin attenuates sympathetic remodeling in chronic heart failure mice via 
      regulating miR-124.
PG  - 359-365
LID - S0006-291X(19)31928-X [pii]
LID - 10.1016/j.bbrc.2019.10.038 [doi]
AB  - AIMS: 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. MAIN METHODS: 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. KEY 
      FINDINGS: 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. 
      SIGNIFICANCE: 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.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Liu, Wen-Lin
AU  - Liu WL
AD  - Affiliated Hospital of Guangdong Medical University; Clinical Research Center of 
      Affiliated Hospital of Guangdong Medical University.
FAU - Liu, Qiang
AU  - Liu Q
AD  - Affiliated Hospital of Guangdong Medical University; Clinical Research Center of 
      Affiliated Hospital of Guangdong Medical University. Electronic address: 
      liuqiangmd1@yeah.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191008
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cardiotonic Agents)
RN  - 0 (GAP-43 Protein)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn124 microRNA, mouse)
RN  - 0 (Naphthoquinones)
RN  - 0 (Slc18a3 protein, mouse)
RN  - 0 (Vesicular Acetylcholine Transport Proteins)
RN  - 3IK6592UBW (shikonin)
SB  - IM
EIN - Biochem Biophys Res Commun. 2022 Aug 27;618:153-154. PMID: 35732545
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Chronic Disease
MH  - Constriction, Pathologic
MH  - GAP-43 Protein/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Heart Failure/*drug therapy/genetics/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Myocardium/metabolism/pathology
MH  - Naphthoquinones/*pharmacology
MH  - Sympathetic Nervous System/drug effects
MH  - Vesicular Acetylcholine Transport Proteins/metabolism
OTO - NOTNLM
OT  - Heart failure
OT  - Shikonin
OT  - Sympathetic remodeling
OT  - miRNA-124
EDAT- 2019/10/13 06:00
MHDA- 2020/07/21 06:00
CRDT- 2019/10/13 06:00
PHST- 2019/09/22 00:00 [received]
PHST- 2019/10/03 00:00 [accepted]
PHST- 2019/10/13 06:00 [pubmed]
PHST- 2020/07/21 06:00 [medline]
PHST- 2019/10/13 06:00 [entrez]
AID - S0006-291X(19)31928-X [pii]
AID - 10.1016/j.bbrc.2019.10.038 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Dec 3;520(2):359-365. doi: 
      10.1016/j.bbrc.2019.10.038. Epub 2019 Oct 8.