AIM:To investigate the role of renal denervation(RDN)in treatment of obesity-related atrial fi-brillation(AF)in rats.METHODS:A high-fat diet AF-susceptible rat model was constructed.The rats in control group was fed with a standard diet,while those in RDN group was subjected to RDN via surgical and chemical ablation.The re-nal tyrosine hydroxylase expression level was detected by Western blot.An in vivo electrophysiological instrument was used to detect the cardiac electrophysiological parameters of rats,including atrial effective refractory period(AERP),AF induction rate,and AF duration.Alterations in cardiac structure and function of the rats were assessed using echocar-diography.PowerLab bioinformatics acquisition system was used to analyze alterations in the tension of the rat cardiac au-tonomic nervous system.Transmission electron microscopy was used to further observe structural changes in the rat atrial mitochondria.The protein levels of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR)were detected by Western blot.Masson staining and HE staining were used to detect the extent of structural changes in the left atrium.RESULTS:(1)Compared with standard diet group,the AF induction rate and duration of the rats fed with a high-fat diet were significantly increased;however,the AERP significantly decreased.RDN reduced the increases in AF induction rate and duration in the rats fed with a high-fat diet,and even restored the AERP.(2)Cardiac low frequency significantly increased whereas cardiac high frequency decreased in heart autonomic nerves of the rats fed with a high-fat diet.After RDN,low frequency was significantly restored,suggesting that RDN could reverse the cardiac autonomic ner-vous system disorder induced by a high-fat diet.(3)Ultrasound results showed that compared with standard diet group,the left atrial diameter and left ventricular end-systolic diameter(LVESD)of the rats fed with high-fat diet were increased,whereas the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased.Af-ter RDN,the LVEF and LVFS of high-fat diet-fed rats increased,whereas the LVESD decreased.Ultrasound results showed that RDN could attenuate the cardiac functional and structural damage induced by a high-fat diet.Masson and HE staining results showed that compared with standard diet group,atrial fibrosis and atrial cardiomyocyte hypertrophy in-creased in high-fat diet-fed rats,while atrial fibrosis was significantly attenuated after RDN.(4)Transmission electron mi-croscopy showed that the functional structure of atrial mitochondria in high-fat diet-fed rats was damaged,with disordered arrangement and increased number of vacuoles.Western blot results showed that mTOR and p-mTOR protein levels in-creased in the left atrium of high-fat diet-fed rats.Mitochondrial autophagy and structural damage were attenuated after RDN.CONCLUSION:Renal denervation may reduce high-fat diet-induced AF susceptibility via alleviating autonomic nervous system disorders and cardiac structural and functional remodeling.

AIM:To explore the expression of calcium binding and coiled-coil domain 2(CALCOCO2)in ani-mal models of atrial fibrillation(AF)and its role and mechanism in reversing atrial remodeling in AF mice.METHODS:Twelve rats and 12 mice were randomly divided into the following 2 groups(n=6 each):saline control group(saline group)and angiotensin Ⅱ(Ang Ⅱ)-induced AF group(Ang Ⅱ group).Western blot and immunohistochemistry(IHC)were used to detect CALCOCO2 expression in rat and mouse atrial muscle tissues.Another 24 mice were randomly divided into 4 groups(n=6 each):saline-oeNC,Ang Ⅱ-oeNC,saline-oeCALCOCO2,and Ang Ⅱ-oeCALCOCO2.An adeno-asso-ciated virus was used to induce CALCOCO2 overexpression in mouse atrial myocardium.Subsequently,transthoracic echocardiography and intracardiac electrophysiological testing were used to compare mouse cardiac function among the 4 groups.Western blot and TUNEL staining were also used to evaluate the effect of CALCOCO2 on apoptosis of cardiomyo-cytes in AF models.Additionally,IHC was used to assess the effect of CALCOCO2 on the levels of oxidative stress-related proteins[NADPH oxidase 2(NOX2)and NOX4]and fibrosis-related proteins[collagen type Ⅰ(Col Ⅰ),connexin 40(Cx40)and α-smooth muscle actin(α-SMA)]in AF atrial myocardium.RESULTS:The CALCOCO2 protein level in the atrial myocardium of rats and mice was significantly decreased in Ang Ⅱ group compared with saline group,as detected by Western blot and IHC(0.19±0.01 vs 0.32±0.03 for rats,0.37±0.10 vs 1.00±0.10 for mice,P<0.01).Compared with Ang Ⅱ-oeNC group,the mice in Ang Ⅱ-oeCALCOCO2 group exhibited decreased left atrial inner diameter,shorter AF duration,and increased ejection fraction(P<0.05).Semi-quantitative analysis of TUNEL staining revealed a signifi-cantly decreased apoptosis rate of mouse atrial myocytes in Ang Ⅱ-oeCALCOCO2 group compared with Ang Ⅱ-oeNC group(0.30±0.06 vs 0.61±0.03,P<0.01),which was consistent with the Western blot trend of apoptosis-related proteins such as BAX(1.94±0.34 vs 3.14±0.34,P<0.05)and cleaved caspase-3(2.19±0.41 vs 3.52±0.55,P<0.05).The semi-quantitative results of IHC and immunofluorescence revealed significantly increased levels of oxidative stress-related pro-teins(NOX2 and NOX4)and fibrosis-related proteins(Col Ⅰ and α-SMA),as well as decreased Cx40 levels,in Ang Ⅱ-oeNC group compared with saline-oeNC group.However,the expression levels of these proteins were significantly re-versed after CALCOCO2 overexpression(all P<0.05).CONCLUSION:Overexpression of CALCOCO2 reverses AF-in-duced electrical and structural remodeling by inhibiting the oxidative stress,apoptosis and fibrosis in mouse atrial tissues.

AIM:To investigate the role of renal denervation(RDN)in treatment of obesity-related atrial fi-brillation(AF)in rats.METHODS:A high-fat diet AF-susceptible rat model was constructed.The rats in control group was fed with a standard diet,while those in RDN group was subjected to RDN via surgical and chemical ablation.The re-nal tyrosine hydroxylase expression level was detected by Western blot.An in vivo electrophysiological instrument was used to detect the cardiac electrophysiological parameters of rats,including atrial effective refractory period(AERP),AF induction rate,and AF duration.Alterations in cardiac structure and function of the rats were assessed using echocar-diography.PowerLab bioinformatics acquisition system was used to analyze alterations in the tension of the rat cardiac au-tonomic nervous system.Transmission electron microscopy was used to further observe structural changes in the rat atrial mitochondria.The protein levels of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR)were detected by Western blot.Masson staining and HE staining were used to detect the extent of structural changes in the left atrium.RESULTS:(1)Compared with standard diet group,the AF induction rate and duration of the rats fed with a high-fat diet were significantly increased;however,the AERP significantly decreased.RDN reduced the increases in AF induction rate and duration in the rats fed with a high-fat diet,and even restored the AERP.(2)Cardiac low frequency significantly increased whereas cardiac high frequency decreased in heart autonomic nerves of the rats fed with a high-fat diet.After RDN,low frequency was significantly restored,suggesting that RDN could reverse the cardiac autonomic ner-vous system disorder induced by a high-fat diet.(3)Ultrasound results showed that compared with standard diet group,the left atrial diameter and left ventricular end-systolic diameter(LVESD)of the rats fed with high-fat diet were increased,whereas the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased.Af-ter RDN,the LVEF and LVFS of high-fat diet-fed rats increased,whereas the LVESD decreased.Ultrasound results showed that RDN could attenuate the cardiac functional and structural damage induced by a high-fat diet.Masson and HE staining results showed that compared with standard diet group,atrial fibrosis and atrial cardiomyocyte hypertrophy in-creased in high-fat diet-fed rats,while atrial fibrosis was significantly attenuated after RDN.(4)Transmission electron mi-croscopy showed that the functional structure of atrial mitochondria in high-fat diet-fed rats was damaged,with disordered arrangement and increased number of vacuoles.Western blot results showed that mTOR and p-mTOR protein levels in-creased in the left atrium of high-fat diet-fed rats.Mitochondrial autophagy and structural damage were attenuated after RDN.CONCLUSION:Renal denervation may reduce high-fat diet-induced AF susceptibility via alleviating autonomic nervous system disorders and cardiac structural and functional remodeling.