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Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function

BACKGROUND: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether T...

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Autores principales: Yuan, Guo-Qiang, Gao, Song, Geng, Yong-Jian, Tang, Yao-Ping, Zheng, Min-Juan, Shelat, Harnath S, Collins, Scott, Wu, Han-Jing, Wu, Yi-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850670/
https://www.ncbi.nlm.nih.gov/pubmed/29483388
http://dx.doi.org/10.4103/0366-6999.226063
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author Yuan, Guo-Qiang
Gao, Song
Geng, Yong-Jian
Tang, Yao-Ping
Zheng, Min-Juan
Shelat, Harnath S
Collins, Scott
Wu, Han-Jing
Wu, Yi-Ling
author_facet Yuan, Guo-Qiang
Gao, Song
Geng, Yong-Jian
Tang, Yao-Ping
Zheng, Min-Juan
Shelat, Harnath S
Collins, Scott
Wu, Han-Jing
Wu, Yi-Ling
author_sort Yuan, Guo-Qiang
collection PubMed
description BACKGROUND: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. METHODS: After intragastric administration of TXL (0.1 ml/10 g body weight) to C57BL/6J wild-type mice (n = 8) and ApoE-/- mice (n = 8), total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate (HR), left ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and left ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity (PSV), end diastolic flow velocity, and mean flow velocity (MFV) were measured. The pulsatility index (PI) and resistant index were calculated in order to evaluate the vascular elasticity and resistance. The endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor (VEGF). Immunohistochemical detection was performed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P < 0.05 was considered statistically significant. RESULTS: Although there was no significant decrease of cholesterol level (F = 2.300, P = 0.240), TXL inhibited the level of triglyceride and VLDL (F = 9.209, P = 0.024 and F = 9.786, P = 0.020, respectively) in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS (all P < 0.05). TXL enhanced aortic PSV and MFV (F = 10.774, P = 0.024 and F = 11.354, P = 0.020, respectively) and reduced PI of ApoE-/- mice (1.41 ± 0.17 vs. 1.60 ± 0.17; P = 0.037). After incubation with 10 μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% ± 3%, significantly higher than control group mice (F = 9.280, P = 0.040). TXL also restrain the angiogenesis of ApoE-/- mice aorta (F = 21.223, P = 0.010). Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice (54.0 ± 3.0/mm(2) vs. 75.0 ± 2.0/mm(2); F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mm(2) vs. 54.0 ± 3.0/mm(2); F = 11.929, P = 0.020) in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot (F = 20.247, P = 0.004). CONCLUSIONS: TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat to lessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity; improves endothelium-dependent vasodilatation; restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.
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spelling pubmed-58506702018-03-21 Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function Yuan, Guo-Qiang Gao, Song Geng, Yong-Jian Tang, Yao-Ping Zheng, Min-Juan Shelat, Harnath S Collins, Scott Wu, Han-Jing Wu, Yi-Ling Chin Med J (Engl) Original Article BACKGROUND: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. METHODS: After intragastric administration of TXL (0.1 ml/10 g body weight) to C57BL/6J wild-type mice (n = 8) and ApoE-/- mice (n = 8), total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate (HR), left ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and left ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity (PSV), end diastolic flow velocity, and mean flow velocity (MFV) were measured. The pulsatility index (PI) and resistant index were calculated in order to evaluate the vascular elasticity and resistance. The endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor (VEGF). Immunohistochemical detection was performed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P < 0.05 was considered statistically significant. RESULTS: Although there was no significant decrease of cholesterol level (F = 2.300, P = 0.240), TXL inhibited the level of triglyceride and VLDL (F = 9.209, P = 0.024 and F = 9.786, P = 0.020, respectively) in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS (all P < 0.05). TXL enhanced aortic PSV and MFV (F = 10.774, P = 0.024 and F = 11.354, P = 0.020, respectively) and reduced PI of ApoE-/- mice (1.41 ± 0.17 vs. 1.60 ± 0.17; P = 0.037). After incubation with 10 μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% ± 3%, significantly higher than control group mice (F = 9.280, P = 0.040). TXL also restrain the angiogenesis of ApoE-/- mice aorta (F = 21.223, P = 0.010). Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice (54.0 ± 3.0/mm(2) vs. 75.0 ± 2.0/mm(2); F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mm(2) vs. 54.0 ± 3.0/mm(2); F = 11.929, P = 0.020) in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot (F = 20.247, P = 0.004). CONCLUSIONS: TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat to lessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity; improves endothelium-dependent vasodilatation; restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression. Medknow Publications & Media Pvt Ltd 2018-03-05 /pmc/articles/PMC5850670/ /pubmed/29483388 http://dx.doi.org/10.4103/0366-6999.226063 Text en Copyright: © 2018 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Yuan, Guo-Qiang
Gao, Song
Geng, Yong-Jian
Tang, Yao-Ping
Zheng, Min-Juan
Shelat, Harnath S
Collins, Scott
Wu, Han-Jing
Wu, Yi-Ling
Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title_full Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title_fullStr Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title_full_unstemmed Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title_short Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function
title_sort tongxinluo improves apolipoprotein e-deficient mouse heart function
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850670/
https://www.ncbi.nlm.nih.gov/pubmed/29483388
http://dx.doi.org/10.4103/0366-6999.226063
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