Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function

• Published in: Chinese medical journal 2018-03, Vol.131 (5), p.544-552
• Main Authors: Yuan, Guo-Qiang, Gao, Song, Geng, Yong-Jian, Tang, Yao-Ping, Zheng, Min-Juan, Shelat, Harnath, Collins, Scott, Wu, Han-Jing, Wu, Yi-Ling
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apolipoproteins; Apolipoproteins E - blood; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - drug therapy; Blotting, Western; Breast cancer; Cardiovascular disease; Care and treatment; Chinese medicine; Cholesterol; Complications and side effects; Coronary heart disease; Coronary vessels; Development and progression; Drug dosages; Drugs, Chinese Herbal - therapeutic use; Echocardiography; Ejection fraction; Endothelium; Flow velocity; Glucose; Health aspects; Heart; Heart Function; Microvascular Protection; Tongxinluo; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Immunohistochemistry; Internal medicine; Laboratory animals; Lipoproteins, VLDL - blood; Medical schools; Methods; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium - metabolism; Original; Patient outcomes; Physiological aspects; Real-Time Polymerase Chain Reaction; Rodents; Science; Stroke Volume - drug effects; Traditional Chinese medicine; Triglycerides - blood; Vascular endothelial growth factor; Vascular endothelium; 心功能; 老鼠; 胆固醇水平; 电子; 内皮细胞; 流动速度; 聚合酶链反应; 动脉粥样硬化
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.226063

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）, lelt 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 let1 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. Tile 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）. lnamunohistochenaical detection was perlbrmed 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 10μmol/L acetylcholine, the ApoE-/- mice treated with TXL ao