Effects Of Myofibroblasts On The Cardiac Fibrosis Of The Infarcted Rat Heart

To evaluate the dynamic changes of the activation and proliferation of cardiac fibroblasts in infarcted and non-infarcted areas of rat heart. To explore the effects and mechanism of cardiac myofibroblasts (MyoFb) in cardiac fibrosis. MethodsExperimental myocardial infarction was created by left coronary artery ligation in rats. After 24 hours of the above procedure, surviving rats were randomly assigned to the following 2 groups : (1) AMI control group; (2) telmisartan treatment group, the other randomly selected rats were sham-operated group. All groups were terminated at 2, 4, 7, 14, 28 days respectively. At the end of the study, Heart relative weight (heart weight/body weight, HW/BW) was calculated. Morphological characteristics were measured with hematoxylin and eosin (HE), Elastic Van-Gieson, irnmunohistochemistry staining in the infarction and non-infarction myocardium, the activation and proliferation of MyoFb and collagen volume fraction (CVF) were assessed or calculated respectively with compute-assisted image analysis system (Image-Pro Plus, Version: 4.5). Results(1) The mortality of treatment group decreased at 28 days when compared with AMI group (P <0.05); The ratio of HW/BW increased significantly in AMI group on day 7, 14 and 28 when compared with sham-operated group (P all<0.05); but it decreased in treatment group when compared with AMI group (P all<0.05) on day 14,28. (2) In AMI and treatment groups, MyoFb, which were a-SMA Vimentin (VA phenotype) positive, first appeared on day 4; from day 7 to 28, the amount of MyoFb was gradually decreased; the dynamic changes of PCNA positive cells were similar to those observed for MyoFb pattern. On day 28, the percentage of VA and PCNA positive cells were significantly lower in treatment group when compared with AMI group (P all<0.05). (3) In non-infarcted myocardium, there were not significant differences in the percentage of VA and PCNA positive cells among thesham-operated, AMI, treatment groups. (4) From day 4 after AMI, collage accumulation began to increase gradually and became more advanced thereafter, the CVF in treatment group reduced on day 28 when compared with AMI group ( P< 0.05). (5) The CVF increased in AMI group on day 4, 7, 14, 28 when compared with sham-operated group (P all<0.01); But CVF decreased markedly with telmisartan treatment on day 14, 28 when compared with AMI group (P all<0.01) . Conclusions1. Not only activation and proliferation of cardiac fibroblasts but also cardiac fibrosis occurred in the infarcted myocardium of AMI rats. But the above phenomena were attenuated by telmisartan administration; therefore the activation and proliferation of cardiac fibroblasts play an important role in the AMI areas fibrosis.2. Telmisartan treatment improved cardiac remodeling as well as decreased the mortality of AMI rats.3. Cardiac fibrosis also developed in non-infarcted myocardium of AMI rats. But the activation and proliferation of cardiac fibroblasts was not found in the areas. Furthermore the fibrosis of the areas was attenuated by telmisartan treatment, therefore MyoFb might play little role in non-infarcted myocardium fibrosis.