Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy
Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague–Dawley male rats. The RDN/Sha...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/489653 |
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| author | Bin Zhang Xiaorong Li Chu Chen Wanying Jiang Dasheng Lu Qian Liu Kai Wang Yuhao Yan Zhixin Jiang Jie Geng Hai Xu Qijun Shan |
| author_facet | Bin Zhang Xiaorong Li Chu Chen Wanying Jiang Dasheng Lu Qian Liu Kai Wang Yuhao Yan Zhixin Jiang Jie Geng Hai Xu Qijun Shan |
| author_sort | Bin Zhang |
| collection | DOAJ |
| description | Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague–Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson’s trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. Results: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy. |
| first_indexed | 2024-12-13T16:00:10Z |
| format | Article |
| id | doaj.art-20a03d162a1d4bdb9c86b26923016368 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T16:00:10Z |
| publishDate | 2018-05-01 |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-20a03d162a1d4bdb9c86b269230163682022-12-21T23:39:11ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-014662471247910.1159/000489653489653Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic CardiomyopathyBin ZhangXiaorong LiChu ChenWanying JiangDasheng LuQian LiuKai WangYuhao YanZhixin JiangJie GengHai XuQijun ShanBackground/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague–Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson’s trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. Results: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.https://www.karger.com/Article/FullText/489653Renal DenervationMyocardial InfarctionVentricular ArrhythmiaFibrosisConnexin |
| spellingShingle | Bin Zhang Xiaorong Li Chu Chen Wanying Jiang Dasheng Lu Qian Liu Kai Wang Yuhao Yan Zhixin Jiang Jie Geng Hai Xu Qijun Shan Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy Cellular Physiology and Biochemistry Renal Denervation Myocardial Infarction Ventricular Arrhythmia Fibrosis Connexin |
| title | Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy |
| title_full | Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy |
| title_fullStr | Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy |
| title_full_unstemmed | Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy |
| title_short | Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy |
| title_sort | renal denervation effects on myocardial fibrosis and ventricular arrhythmias in rats with ischemic cardiomyopathy |
| topic | Renal Denervation Myocardial Infarction Ventricular Arrhythmia Fibrosis Connexin |
| url | https://www.karger.com/Article/FullText/489653 |
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