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The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy
Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hyperten...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960224/ https://www.ncbi.nlm.nih.gov/pubmed/24647357 http://dx.doi.org/10.1371/journal.pone.0092216 |
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author | Pang, Hui Han, Bing Yu, Tao Peng, Zhen |
author_facet | Pang, Hui Han, Bing Yu, Tao Peng, Zhen |
author_sort | Pang, Hui |
collection | PubMed |
description | Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson’s trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage. |
format | Online Article Text |
id | pubmed-3960224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39602242014-03-24 The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy Pang, Hui Han, Bing Yu, Tao Peng, Zhen PLoS One Research Article Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson’s trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage. Public Library of Science 2014-03-19 /pmc/articles/PMC3960224/ /pubmed/24647357 http://dx.doi.org/10.1371/journal.pone.0092216 Text en © 2014 Pang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pang, Hui Han, Bing Yu, Tao Peng, Zhen The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title | The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title_full | The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title_fullStr | The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title_full_unstemmed | The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title_short | The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy |
title_sort | complex regulation of tanshinone iia in rats with hypertension-induced left ventricular hypertrophy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960224/ https://www.ncbi.nlm.nih.gov/pubmed/24647357 http://dx.doi.org/10.1371/journal.pone.0092216 |
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