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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.
Afiliación
  • Yuan GQ; Department of Collateral Disease, Research Institute of Integrated Traditional Chinese Medicine and Western Medicine of Hebei, Shijiazhuang, Hebei 050035; Department of Cardiovascular Disease, Hebei Yiling Hospital, Shijiazhuang, Hebei 050091, China.
  • Gao S; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Geng YJ; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Tang YP; Center for Cell Signaling, Institute of Molecular Medicine, Houston Health Science Center, The University of TX, Houston, TX 77030, USA.
  • Zheng MJ; Department of Pediatric Cardiology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shelat HS; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Collins S; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Wu HJ; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Wu YL; Department of Collateral Disease, Research Institute of Integrated Traditional Chinese Medicine and Western Medicine of Hebei, Shijiazhuang, Hebei 050035, China.
Chin Med J (Engl) ; 131(5): 544-552, 2018 Mar 05.
Article en En | MEDLINE | ID: mdl-29483388
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/mm2 vs. 75.0 ± 2.0/mm2; F = 16.054, P = 0.010). However, TXL could significantly enhance MVD (65.0 ± 5.0/mm2 vs. 54.0 ± 3.0/mm2; 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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Texto completo: 1 Bases de datos: MEDLINE Medicinas Tradicionales: Medicinas_tradicionales_de_asia / Medicina_china Métodos Terapéuticos y Terapias MTCI: Terapias_biologicas Asunto principal: Apolipoproteínas E / Medicamentos Herbarios Chinos Tipo de estudio: Prognostic_studies Idioma: En Revista: Chin Med J (Engl) Año: 2018 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Medicinas Tradicionales: Medicinas_tradicionales_de_asia / Medicina_china Métodos Terapéuticos y Terapias MTCI: Terapias_biologicas Asunto principal: Apolipoproteínas E / Medicamentos Herbarios Chinos Tipo de estudio: Prognostic_studies Idioma: En Revista: Chin Med J (Engl) Año: 2018 Tipo del documento: Article País de afiliación: China