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Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction
BACKGROUND: Myocardial apoptosis is important in the pathogenesis and progression of myocardial infarction-induced heart failure (MI-HF). Renal sympathetic denervation (RDN) has become a promising therapeutic strategy for the treatment of HF. Previous studies have shown that RDN could improve heart...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941584/ https://www.ncbi.nlm.nih.gov/pubmed/29739333 http://dx.doi.org/10.1186/s12872-018-0828-y |
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author | Wang, Li Song, Lijun Li, Chao Feng, Qiaoli Xu, Mengping Li, Zhuqing Lu, Chengzhi |
author_facet | Wang, Li Song, Lijun Li, Chao Feng, Qiaoli Xu, Mengping Li, Zhuqing Lu, Chengzhi |
author_sort | Wang, Li |
collection | PubMed |
description | BACKGROUND: Myocardial apoptosis is important in the pathogenesis and progression of myocardial infarction-induced heart failure (MI-HF). Renal sympathetic denervation (RDN) has become a promising therapeutic strategy for the treatment of HF. Previous studies have shown that RDN could improve heart function Yao et al. (Exp Ther Med 14:4104-4110, 2017). However, whether and how RDN regulates myocardial apoptosis in MI-HF is unclear. This study sought to evaluate the effects of RDN on cardiac function and apoptosis-related gene expression in MI-HF dogs. METHODS: Eighteen healthy mongrel dogs were randomly divided into control group(n = 6), model group(n = 6) and treatment group(n = 6). MI-HF was established in model group and treatment group by anhydrous alcohol embolization, after heart failure dogs in the treatment group and model group proceeded bilateral renal artery ablation and bilateral renal arteriography, respectively. The cardiac function parameters were evaluated by echocardiographic; the serum NT-BNP level was detected by ELISA; the degree of myocardial fibrosis was observed through masson staining; the expression of MMP-2, MMP-9 in the cardiac were got by immunohistochemistry. TUNEL method was used to observe cardiomyocyte apoptotsis and calculate the apoptosis index (AI). Relative expression of Bcl-2 and Bax, Caspase3 and GRP78 were detected using RT-PCR and Western Blot. Renal artery H&E staining and serum creatinine were conducted to access the efficacy and safety of RDN. RESULTS: Four weeks after RDN, the LVEDD, LVESD and LVEDP decreased, and the LVEF and LVSP increased in the treatment group compared with those in the control group (all P < 0.05). Moreover, NT-BNP, an indicator of cardiac function was decreased. Additionally, MMP-2 and MMP-9 levels in the myocardium decreased significantly in the treatment group. Furthermore, the levels of Bax, and caspase 3 decreased, while the level of Bcl-2 increased. Thus, myocardial apoptosis was attenuated in RDN treated dogs. We also found that the level of GRP78 which is activated in response to endoplasmic reticulum (ER) stress, was decreased. However, serum creatinine levels were not significantly different between the RND-treated dogs and the control dogs. CONCLUSION: Cardiac function was improved by RDN treatment through regulating apoptosis and ER stress in cardiomyocytes in dogs after MI. |
format | Online Article Text |
id | pubmed-5941584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59415842018-05-14 Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction Wang, Li Song, Lijun Li, Chao Feng, Qiaoli Xu, Mengping Li, Zhuqing Lu, Chengzhi BMC Cardiovasc Disord Research Article BACKGROUND: Myocardial apoptosis is important in the pathogenesis and progression of myocardial infarction-induced heart failure (MI-HF). Renal sympathetic denervation (RDN) has become a promising therapeutic strategy for the treatment of HF. Previous studies have shown that RDN could improve heart function Yao et al. (Exp Ther Med 14:4104-4110, 2017). However, whether and how RDN regulates myocardial apoptosis in MI-HF is unclear. This study sought to evaluate the effects of RDN on cardiac function and apoptosis-related gene expression in MI-HF dogs. METHODS: Eighteen healthy mongrel dogs were randomly divided into control group(n = 6), model group(n = 6) and treatment group(n = 6). MI-HF was established in model group and treatment group by anhydrous alcohol embolization, after heart failure dogs in the treatment group and model group proceeded bilateral renal artery ablation and bilateral renal arteriography, respectively. The cardiac function parameters were evaluated by echocardiographic; the serum NT-BNP level was detected by ELISA; the degree of myocardial fibrosis was observed through masson staining; the expression of MMP-2, MMP-9 in the cardiac were got by immunohistochemistry. TUNEL method was used to observe cardiomyocyte apoptotsis and calculate the apoptosis index (AI). Relative expression of Bcl-2 and Bax, Caspase3 and GRP78 were detected using RT-PCR and Western Blot. Renal artery H&E staining and serum creatinine were conducted to access the efficacy and safety of RDN. RESULTS: Four weeks after RDN, the LVEDD, LVESD and LVEDP decreased, and the LVEF and LVSP increased in the treatment group compared with those in the control group (all P < 0.05). Moreover, NT-BNP, an indicator of cardiac function was decreased. Additionally, MMP-2 and MMP-9 levels in the myocardium decreased significantly in the treatment group. Furthermore, the levels of Bax, and caspase 3 decreased, while the level of Bcl-2 increased. Thus, myocardial apoptosis was attenuated in RDN treated dogs. We also found that the level of GRP78 which is activated in response to endoplasmic reticulum (ER) stress, was decreased. However, serum creatinine levels were not significantly different between the RND-treated dogs and the control dogs. CONCLUSION: Cardiac function was improved by RDN treatment through regulating apoptosis and ER stress in cardiomyocytes in dogs after MI. BioMed Central 2018-05-08 /pmc/articles/PMC5941584/ /pubmed/29739333 http://dx.doi.org/10.1186/s12872-018-0828-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Wang, Li Song, Lijun Li, Chao Feng, Qiaoli Xu, Mengping Li, Zhuqing Lu, Chengzhi Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title | Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title_full | Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title_fullStr | Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title_full_unstemmed | Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title_short | Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
title_sort | renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941584/ https://www.ncbi.nlm.nih.gov/pubmed/29739333 http://dx.doi.org/10.1186/s12872-018-0828-y |
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