ABSTRACT
Objective To investigate the remodeling of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation and its possible mechanism.Methods The clinical data and right atrial tissue specimens were obtained from patients who had undergone mitral valve replacement for rheumatic valvular disease or who had undergone thoracotomy for congenital heart disease in the Second People's Hospital of Yibin from Oct.2013 to Oct.2015.According to the heart rhythm characteristics,the specimens obtained from these patients were divided into sinus rhythm group (RHD-SR group,18 cases),paroxysmal atrial fibrillation group (RHD-pAF group,21 cases) and persistent atrial fibrillation group (RHD-cAF group,42 cases).The right atrial tissue specimens obtained from those who had undergone thoracotomy for congenital heart disease with sinus rhythm were taken as the control group(CHD-SR group,21 cases).The structures of atrial tissues were observed under a light microscope.The picric acidsirius red staining was used to detect collagen volume fraction (CVF) of type Ⅰ and Ⅲ collagen and the type Ⅰ /Ⅲ collagen CVF ratio.The expressions of TGF-β1 protein and mRNA were detected by using Western blot and reverse transcription polymerase chain reaction (RT-PCR).Results The left atrial diameter (LAd) in the RHD-cAF group was significantly higher than that in the RHDSR group (P＜0.05),but no statistically significant difference was found in other clinical data among these groups (P＞0.05).The results of picric acid-sirius red staining demonstrated that the volume fraction of type Ⅰ and type Ⅲ1 collagen and the ratio of type Ⅰ /Ⅲ collagen were increased in CHD-SR group,RHD-SR group,RHD-pAF group and RHD-cAF group,gradually,there were statistically significant differences (P＜0.05),The expression levels of TGF-β1 protein and mRNA were increased gradually in CHD-SR,RHD-SR,RHD-pAF and RHD-cAF groups (P＜0.05).Conclusion Atrial fibrosis remodeling is an important mechanism of atrial fibrillation in patients with RHD.High expression of TGF-β1 may be involved in the remodeling of atrial fibrosis.
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Objective To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and the possible mechanisms involved.Methods The myocardial infarction rat model was reproduced.Twenty-four hours after infarction,the survived rats were randomly divided into myocardial infarction group(MI group,n=9),simvastatin 10mg group [10mg/(kg?d),Sim1 group;n=8],simvastatin 20mg group [20mg/(kg?d),Sim2 group;n=10] and simvastatin 40mg group [40mg/(kg?d),Sim4 group;n=9].A sham-operated group(Sham group;n=10) served as control.Four weeks later,the serum lipid level,hemodynamic indexes and left ventricular weight index(LVWI) were measured.The changes in rats' myocardial tissue were observed with HE staining;the cross-sectional area of myocardial cells was calculated.The expressions of transforming growth factor ?1(TGF-?1) and TGF-?-activated kinase 1(TAK1) in non-infarction area were determined by Western blotting and reverse transcription polymerase chain reaction(RT-PCR).Results The hemodynamic indexes,LVWI,cross-sectional area of myocardial cells and the pathological changes were improved,and mRNA and protein expressions of TGF-?1 and TAK1 were down-regulated significantly in the 3 Sim-treated groups compared with that in MI group.The indices mentioned above were significantly different in Sim2 and Sim4 group compared with Sim4 group(P0.05).Conclusion The inhibitory effect of simvastatin on ventricular remodeling after acute myocardial infarction is independent of its lipid-regulating effect,but possibly attributed to its action in inhibiting the TGF-?1/AK1 signal transduction.Within the concentration of 20mg/(kg?d),the therapeutic efficacy of simvastatin may be more obvious with an increase in its dosage.
ABSTRACT
0.05).Compared with those in Sham group,LVWI,the typeⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were increased significantly in MI group.Compared with those in MI group,the LVWI,the type ⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were decreased significantly in Sim groups(but higher than those in Sham group).Compared with MI groups,left ventricular function in rats treated with simvastatin was also obviously improved.(2) Contrasted to those in MI group,the expressions of TGF-?1 and Smad3 were down-regulated in simvastatin treatment groups(but higher than those in Sham group).Conclusions Sim can ameliorate ventricular remodeling and ventricular function in rats induced by MI,and the mechanisms can be independent of its lipid-lowering and associated with inhibition of TGF-?1/Smad3 signal transduction.