Endothelin-1 regulates SOCC/TGF-β and involved in atrial fibrosis in rats with atrial fibrillation
Objective To investigate the effect and mechanism of endothelin-1(ET-1)on atrial fibrosis in Atrial fibrillation(AF)rats.Methods Fourteen adult male SD rats were randomly divided into normal control(NC)group and Atrial fibrillation(AF)group.The rat model of Atrial fibrillation was established by injecting 0.1 ml/100g CaCl2-Ach mixture into the tail vein once a day for one week.The control group was injected with the same dose of normal saline.An electrocardiogram of normal or atrial fibrillation was recorded on the first day and the eighth day in each group,and echocardiography was used to monitor atrial size and cardiac function.The fibrosis of atrial was observed using Masson and HE staining.The expression of endothelin-1(ET-1),collagen-I(Col-I),transforming growth factor-β(TGF-β)and the store operated calcium channel(SOCC)protein Orai1,stromal in-teraction molecule 1(STIM1)in atrial tissue were detected by Western blot.HL-1 cells were cultured and treated with gradient concentration of ET-1 for 24 hours.Western blot was used to observe changes in the expression of TGF-β,Orai1 and STIM1 proteins in ET-1/SOCC/TGF-β signaling pathway of HL-1 cells.Small interfering RNA(siRNA)transfection method was used to knock down the expression of Orai1 in HL-1 cells,then the cells were treated with appropriate concentrations of ET-1 for 24 hours,and the expression of TGF-β protein in HL-1 cells was detected by Western blot.Results Compared with the control group,echocardiography showed a significant in-crease in left atrial diameter(LAD)of the heart in atrial fibrillation rats(P<0.05).The HE and Masson staining results showed significant fibrosis in the myocardial tissue of AF group rats(P<0.05),and the Western blot re-sults indicated the expression of ET-1,Orai1,STIM1,TGF-β and COL-Ⅰ in the myocardial tissue of AF group significantly increased compared to the NC group(P<0.05).After ET-1 treatment of HL-1 cells,the protein ex-pression of Orai1,STIM1and TGF-β increased(P<0.05),while knocking down Orai1 in HL-1 cells,ET-1 treat-ment no longer caused the expression of TGF-β a significant upregulation.Conclusion AF caused by atrial fibril-lation results in a significant increase in ET-1 expression in atrial tissue,and ET-1/SOCC/TGF-β signal pathway promotes atrial fibrillation and fibrosis.
万方数据
维普
