04 July 2016 : Animal Research
Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A)
Ling FeiBCDEF, Jun ZhangA, Heping NiuBCDEF, Chen YuanBCDEF, Xiaoli MaBCDEFDOI: 10.12659/MSM.896983
Med Sci Monit 2016; 22:2324-2334
Abstract
BACKGROUND: The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect.
MATERIAL AND METHODS: SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro.
RESULTS: Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3’ UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05).
CONCLUSIONS: miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by.
Keywords: Biomarkers - metabolism, Creatine Kinase, MB Form - metabolism, HEK293 Cells, Heart Injuries, Myocardial Infarction - pathology, Myocardium - metabolism, Random Allocation, Rosuvastatin Calcium - pharmacology, Stroke Volume - physiology, Vascular Endothelial Growth Factor A - metabolism, Ventricular Function, Left - physiology
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