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BACKGROUND:A number of studies have shown that bone marrow mesenchymal stem cells can survive in the infarcted myocardium and improve cardiac function. OBJECTIVE:To investigate the effects of al ogeneic rat bone marrow mesenchymal stem cells on heart failure in acute myocardial infarction models of rats and possible mechanisms. METHODS:Rat bone marrow mesenchymal stem cells were isolated from the bone marrow of 39 male Wistar rats by density gradient centrifugation with Percol . After ligating anterior descending coronary artery, 39 female Wistar rats were randomly divided into three groups:control group (Dulbecco’s modified Eagle’s medium, n=12), mesenchyma stem cells group (n=15) and mononuclear cells group (n=12). Eight weeks later, hemodynamics and left ventricular function were measured. Histopathological and immunohistochemical examinations were performed. RESULTS AND CONCLUSION:Compared with the control group, left ventricular end diastolic pressure, left ventricular relative weight, the col agen volume fraction of type I and type III in the infarction zone of the left ventricle were al significantly decreased, in contrast to ±dp/dtmax,-dp/dtmax/left ventricular systolic pressure, body weight and vascular density in infarction zone were al significantly increased both in mesenchymal stem cells group and mononuclear cells group. There were no significant differences between two treatment groups except for interventricular septal thickness and vascular density in non-infarction zone. 5-Bromo-2'-deoxyuridine positive cells were observed in the infarction area of mesenchyma stem cells group but no positive cells in mononuclear cells group. Some bal-like cellmasses were found positively stained with desmin and cardiac troponin T. Results have suggested that embedded bone marrow mesenchymal stem cells survived in exogenous host hearts. The therapy of mononuclear cells and mesenchymal stem cells could limit the left ventricular remodeling after acute myocardial infarction and improve left ventricular function through angiogenesis inducing and col agen deposition decreasing.
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@#Objective To investigate the effect of hepatocyte growth factor (HGF) on mitral regurgitation caused by acute myocardial infarction in canines.Methods The acute myocardial infarction model was established by ligating proximal left anterior descending coronary artery (LAD) with 13 hybrid canines. The myocardial infarction model was successfuly established in 12 animals and those were randomly divided into the HGF-group and control group with 6 animals in each group. Canines of the HGF-group were injected with pc-DNA3-HGF 1 ml (about 300 μg) at the margin of infarcted myocardial and animals of the control group were injected with equal volume saline. The data were measured through echocardiography in the 1st, 4th and 8th week after ligation as following parameters: left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left atrial area, mitral regurgitation area and the ratio of left atrial area to mitral regurgitation area. Left ventricular myocardium specimens were obtained in the 8th week after ligation and stained with hematoxylin and eosin for histological examination or with picrosirius red staining to assess the collagen content.Results Compared with the control group, LVEF in the HGF-group increased in the 4th week after ligation; LVEF significantly improved and LVESV decreased in the 8th week after ligation ( P<0.05). In the 8th week after ligation, left atrial area, mitral regurgitation area and the ratio of left atrial area to mitral regurgitation area in the HGF-group were lower than that in the control group. In the HGF-group, neovascularization and fewer scars were observed histologically. Compared with the control group, the HGF-group showed higher capillary density in margin of infarcted area by factor Ⅷ-related immunohistochemistry staining ( P<0.01).Conclusion HGF gene can improve cardiac function and relieve mitral regurgitation after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, diminishing myocardiolysis and scarring.
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Background and objectives To investigate the effect of hepatocyte growth factor (HGF) on left ventricular (LV) remodeling after acute myocardial infarction (AMI). Methods AMI was produced by ligation of proximal left anterior descending coronary artery(LAD) in 12 mongrel canines. These animals were randomized into 2 groups. In HGF group (n=6), canines were injected with pcDNA3-HGF lml (about 300ug) at the margin of infarcted myocardium; in control group (n=6) canines were injected with equal volume of normal saline. Cardiac function and left ventricular remodeling were evaluated with echocardiography at 1, 4, 8 weeks after MI. LV myocardium specimens were obtained at 8 weeks and stained with hematoxylin and eosin for histological examination or with sirius red to assess the collagen content. Results Compared with control group, LVEF in HGF group was significantly higher at 4 weeks (49.61+6.66 vs 39.84+6.39; P＜0.05) and at 8 weeks (51.57+8.53 vs 40.61+7.67; P＜0.05) after AMI, while LVESV was significantly lower in HGF group than that in control group at 8 weeks after AMI (18.98+3.47 vs 25.66+5.86; P＜0.05). Posterior left ventricular wall thickness decreased significantly from 1 wk to 8 wks after AMI in control group, while remained unchanged in HGF group. Compared with control group, histological examination showed more neovascularization and less scar, and sirius red staining indicated higher volume of type Ⅲ collagen (7.10±4.06% vs 3.77±1.09%; P＜0.05) and lower collagen Ⅰ/Ⅲ ratio value (1.11±0.52 vs 2.94±2.48; P＜0.05)in HGF group. Conclusion HGF gene transfer might improve cardiac function and LV remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, and reducing myocardial scarring.
