Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats

The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper-innervation and decrease the vulnerability to malignant ventricular tachyarrhy...

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Main Authors: Chen, Ren-Hua, Li, Yi-Gang, Jiao, Kun-Li, Zhang, Peng-Pai, Sun, Yu, Zhang, Li-Ping, Fong, Xiang-Fei, Li, Wei, Yu, Yi
Format: Online
Language:English
Published: Blackwell Publishing Ltd 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822813/
id pubmed-3822813
recordtype oai_dc
spelling pubmed-38228132014-12-03 Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats Chen, Ren-Hua Li, Yi-Gang Jiao, Kun-Li Zhang, Peng-Pai Sun, Yu Zhang, Li-Ping Fong, Xiang-Fei Li, Wei Yu, Yi Original Articles The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper-innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus-mediated overexpression of Sema3a (SLV, n = 13) groups. Sham-operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth-associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper-reinnervation after infarction. Blackwell Publishing Ltd 2013-05 2013-05-27 /pmc/articles/PMC3822813/ /pubmed/23711091 http://dx.doi.org/10.1111/jcmm.12035 Text en Copyright © 2013 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chen, Ren-Hua
Li, Yi-Gang
Jiao, Kun-Li
Zhang, Peng-Pai
Sun, Yu
Zhang, Li-Ping
Fong, Xiang-Fei
Li, Wei
Yu, Yi
spellingShingle Chen, Ren-Hua
Li, Yi-Gang
Jiao, Kun-Li
Zhang, Peng-Pai
Sun, Yu
Zhang, Li-Ping
Fong, Xiang-Fei
Li, Wei
Yu, Yi
Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
author_facet Chen, Ren-Hua
Li, Yi-Gang
Jiao, Kun-Li
Zhang, Peng-Pai
Sun, Yu
Zhang, Li-Ping
Fong, Xiang-Fei
Li, Wei
Yu, Yi
author_sort Chen, Ren-Hua
title Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
title_short Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
title_full Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
title_fullStr Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
title_full_unstemmed Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
title_sort overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats
description The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper-innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus-mediated overexpression of Sema3a (SLV, n = 13) groups. Sham-operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth-associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper-reinnervation after infarction.
publisher Blackwell Publishing Ltd
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822813/
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