| Atrial fibrillation(AF)is the most serious atrial electrical activity disorder and it is a serious threat to human health.The pathogenesis of AF is still intricate.Atrial electrical remodeling,structural remodeling and Cardiac autonomic nervous system disorders played the critical role in atrial fibrillation.As the salient characteristic of atrial remodeling,atrial fibrosis attracted more and more attention.Atrial fibrosis is the final outcome of a variety of cardiovascular diseases.Atrial fibrillation will be more difficult to reverse and treatment once atrial fibrosis.Therefore,to explore the mechanisms of atrial fibrosis and find new signaling pathways of fibrosis will provide a new and effective means for the prevention and treatment of AF.Endothelin-1(ET-1)is an important vasoactive peptides.The Recent studies have shown that the expression of ET-1 in atrial tissue and peripheral blood is significantly increased in patients with AF.And ET-1 can be used to the prediction of AF recurrence after radiofrequency ablation.These studies suggested that ET-1 played an important role in the pathogenesis of AF,but the specifically mechanism has not been reported.Platelet-derived growth factor-B(PDGF-B)is one of the most important fibrogenic cytokines and it plays an important role in the process of atrial fibrosis.Studies had shown that ET-1 can stimulate glomerular mesangial cells to secrete PDGF.But whether ET-1 contributes to atrial:fibrosis by stimulating PDGF-B secretion in atrial myocardial cells needs further research.In our study,the right atrial appendage tissue was collected from 72 patients with sinus rhythm(SR)or AF in thoracotomy.Tissue morphological changes were observed by HE staining and collagen fibers deposition was observed by Masson staining.The mRNA and protein expression of ET-1,PDGF-B and Collagen Type I(COL1)were measured by real time quantity polymerase chain reaction(RT-qPCR),Western-blot and immune histochemistry(IHC).Then we compared the mRNA and protein expression of PDGF-B in H9c2 cell which was stimulated with ET-1 in different concentrations and different time,and which was cultured with ET-1 combined non-selective endothelin receptor antagonist Sulfafurazole(SIZ).The results of our study show that:(1)Compared with SR group(1.2197±0.8872),the mRNA expression of ET-1 was significantly higher in AF group(2.83000±2.2764),P<0.01;and the protein expression of ET-1 is also significantly higher in AF group(0.8349±0.2413)than in SR group(0.2860±0.0828),P<0.01.(2)The mRNA expression of PDGF-B was significantly higher in AF group(2.5675±2.3481)than in SR group(1.5674±0.8314),P<0.05;and the protein expression of PDGF-B is also significantly higher in AF group(0.8074±0.2407)than in SR group(0.3806±0.1049),P<0.01.(3)The mRNA expression of collagen type I alpha 1(COL1A1)was significantly higher in AF group(3.3761±1.5977)than in SR group(1.6292±0.8329),P<0.05;and the protein expression of COL1A1 is also significantly higher in AF group(0.6524±0.2097)than in SR group(0.31231±0.1218),P<0.05.(4)The experiment result present a significantly positive correlation on the protein expression of ET-1 and collagen I(r=0.580,P<0.01)and a significantly positive correlation on the protein expression of ET-1 and PDGF-B(r=0.619,P<0.01).(5)Masson staining showed collagen fibers deposition in RAA of AF group was significantly higher than the SR group.(6)ET-1 can stimulate H9c2 cell to secrete PDGF-B and shown a concentration-dependent and time-dependent manner.SIZ can reduce effect on ET-1 stimulating the H9c2 cell to secrete PDGF-B.In summary,ET-1 plays an important role in atrial fibrosis in atrial fibrillation,which may promote atrial fibrosis by regulating PDGF-B involved in the occurrence of AF. |
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