| Atrial fibrillation(AF)is a common arrhythmia.The mechanism of AF is not clear.It is confirmed that old age,inflammation,obesity,and oxidative stress are involved in the pathogenesis of AF.Chemokines,subdivided into four families(C,CC,CXC,and CX3C),has a regulatory role in inflammation.Fractalkine is the sole member of the CX3 C chemokine family and is closely correlated with inflammation.Adropin,a newly found regulatory protein,is encoded by Enho gene(energy homeostasis associated).Adropin plays an important role in adiposity,insulin resistance,glucose and lipid metabolism.Adropin suppressed tumor necrosis factor α-induced THP1 monocyte adhesion to human umbilical vein endothelial cells.This indicates the anti-inflammatory role of adropin.As we know,inflammation is a clear mechanism of AF.It is speculated that fractalkine and adropin may be correlated with AF development via the effects on the inflammation.Statins,the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,were widely used in clinical as lipid-lowering drugs.It not only has the effect of lowering lipids and stabilizing plaque,but also has anti-inflammatory,antioxidant properties and improved endothelial function.Current clinical studies and animal experiments showed that statins have a certain preventive effect on atrial fibrillation.The pathogenesis of AF is related to the inflammatory response.However,the molecular mechanism of statins in preventing atrial fibrillation remains unclear,and whether they are related to their anti-inflammatory effects remains to be studied.In our present study,animal experiments and clinical trials were conducted to determine the expression levels of fractalkine and adropin in atrial fibrillation,and to observe the effects of statins on fractalkine and adropin in atrial fibrillation and the relationship between atrial fibrillation,fractalkine,adropin and atorvastatin.Part oneObjective:This study aims to determine the change of fractalkine and adropin in a canine model of AF.Method:12 healthy dogs were utilized in this study.They were divided into AF group and the control group(6 dogs in each group).Rapid atrial pacing method was used to establish the canine model of AF.10 weeks later,blood was abstracted through femoral artery puncture and centrifuged.Serum was collected and stored,then was used to examine fractalkine and adropin concentrations.Atrial tissues were also collected.Then the expression levels of fractalkine and adropin in atrial tissues were determined using realtime-polymerase chain reaction(PCR)and western blot methods.Results:AF dog showed higher serum fractalkine concentrations and lower serum adropin concentrations compared with the control group.Realtime-PCR and western blot indicated that left and right atrial tissues of AF dog both showed higher fractalkine expression levels and lower adropin expression levels compared with the control group.Conclusion:The expression of fractalkine is elevated,while the expression of adropin is decreased during AF condition.This indicates that fractalkine and adropin may be involved in the pathophysiological mechanism of AF.Part twoObjective:This study aims to determine the effects of atorvastatin on the fractalkine and adropin levels in a canine model of AF.Method:18 healthy dogs were utilized in this study.They were divided into the control group,AF group,and atorvastatin group(6 dogs in each group).Rapid atrial pacing method was used to establish the canine model of AF.The dogs in AF group were treated with atorvastatin at a dose of 20 mg/day.10 weeks later,blood was abstracted through femoral artery puncture and centrifuged.Serum was collected and stored,then was used to examine fractalkine and adropin concentrations.Atrial tissues were also collected.Then the expression levels of fractalkine and adropin in atrial tissues were determined using realtime-PCR and western blot methods.Results:AF dog showed higher serum fractalkine concentrations and lower serum adropin concentrations compared with the control group.In addition,the dogs in atorvastatin group showed decreased serum fractalkine concentrations and higher serum adropin concentrations compared with the AF group.Realtime-PCR and western blot indicated that atrial tissues of AF dog showed higher fractalkine expression levels and lower adropin expression levels compared with the control group.In addition,left and right atrial tissues of atorvastatin group both showed decreased m RNA and protein expression levels of fractalkine and higher m RNA and protein expression levels of adropin compared with the AF group.Conclusion:Atorvastatin treatment contributes to decreased fractalkine expression and elevated adropin expression.This indicate that atorvastatin may improve AF through the effects on the expression of fractalkine and adropin.Part threeObjective:The aim of this study is to determine serum fractalkine and adropin concentrations in AF patients,and then to analyze the association of serum fractalkine and adropin with the risk of AF,as well as the correlation of serum fractalkine and adropin with other clinical characteristics.Method:344 AF patients and 210 healthy controls were enrolled in this study.Then AF patients were divided into paroxysmal AF subgroup,persistent AF subgroup,and permanent AF subgroup.The serum were collected and serum fractalkine,adropin and C-reactive protein(CRP)concentrations in AF and control groups.Left atrial diameter(LAD)was evaluated using the two-dimensional and Doppler echocardiography.Results:AF patients showed higher serum fractalkine concentrations and lower serum adropin concentrations compared with healthy controls.Logistic regression analysis confirmed that serum fractalkine and adropin concentrations were associated with the risk of AF,respectively.There were elevated serum fractalkine concentrations and decreased serum adropin concentrations in persistent AF group than those in paroxysmal AF group.Permanent AF patients had significantly higher serum fractalkine concentrations and reduced serum adropin concentrations compared with persistent and paroxysmal AF patients.Simple linear regression analyses showed that serum fractalkine in AF patients were correlated with body mass index(BMI),LAD,CRP and NT-pro BNP.Multiple stepwise regression analysis showed that BMI,LAD and NT-pro BNP remained to be associated with serum fractalkine.Simple linear regression analyses showed that serum adropin in AF patients were negatively correlated with BMI,systolic blood pressure(SBP),LAD,CRP and NT-pro BNP.Multiple stepwise regression analysis showed that BMI,SBP,LAD,CRP and NT-pro BNP remained to be associated with serum adropin.Moreover,serum fractalkine were negatively correlated with serum adropin in AF patients.Conclusion:Eleveted serum fractalkine concentrations and decreased serum adropin concentrations are correlated with the risk of AF.Serum fractalkine and adropin were correlated with metabolic syndrome,inflammation,and atrial remodelling.Part fourObjective:This study aims to determine the effects of atorvastatin on serum fractalkine and adropin concentrations in AF patients.Method:344 AF patients were enrolled in this study.Then AF patients were divided into paroxysmal AF subgroup,persistent AF subgroup,and permanent AF subgroup.All AF patients were treated with atorvastatin(20mg/day)for 3 months.Three months later,the serum levels of fractalkine,adropin,CRP,NT-pro BNP and LAD in AF patients were examined to determine.Results:Serum fractalkine concentrations were significantly decreased,while serum adropin concentrations were significantly elevated in AF patients after atorvastatin treatment for three months.In addition,CRP,NT-pro BNP and LAD were significantly elevated in AF patients after atorvastatin treatment for three months.Paroxysmal AF subgroup,persistent AF subgroup,and permanent AF subgroup all showed decreased serum fractalkine concentrations and elevated serum adropin concentrations after atorvastatin treatment.Moreover,the three subgroups all showed decreased CRP,NT-pro BNP,and LAD after atorvastatin treatment.Conclusion:Atorvastatin treatment contributes to decreased serum fractalkine concentrations,elevated serum adropin concentrations and decreased serum CRP,NT-pro BNP,and LAD.This indicate that atorvastatin may improve AF through the effects on fractalkine and adropin. |
