A Study Of Chloride Channels Gene Expression In Human Atrial Tissue And Its Relationship With Atrial Fibrillation

Objective The purpose of this study is to investigate gene expression ofchloride channels ClC-1,ClC-2,ClC-3 and CFTR in human atrial tissue and itsrelationship with atrial fibrillation(AF).Methods Right atrial appendages specimen were obtained from 33 patients withchronic AF(CAF group) ,7 with paroxysmal AF(PAF group) and 31 matched controlsin sinus rhythm (SR group) who underwent open-heart surgery. In this study ,weused semi-quantitative polymerase chain reaction(RT-PCR)in combination withimmunohistochemistry to examine the mRNA expression and protein distributionof ClC-1,ClC-2,ClC-3 and CFTR channels in atrial tissue.Results (1) chloride channels ClC-1,ClC-2,ClC-3 and CFTR do express in humanatrial tissue.(2)The content of ClC-1 mRNA in CAF group(1.25±0.18) wassignificantly higher than that in SR group(1.01±0.13)(P<0.001),There was nosignificant difference between PAF group(1.05±0.22) and SR group although thecontent of ClC-1 mRNA was slightly higher than that in SR group(P>0.05). Thesignificant difference was observed between PAF group and SR group(P<0.01).ClC-1 expression at mRNA level was positively correlated with left atrialdimension and AF duration[(r=0.344,P=0.003)(r=0.405,P<0.001)].The ClC-1protein expression in CAF group(55.37±5.14) was significantly higher thanthat in SR group(41.64±6.37)(P<0.001),There was no significant differencebetween PAF group(44.40±3.94) and SR group although the ClC-1 proteinexpression was slightly higher than that in SR group(P>0.05). The significantdifference was also observed between PAF group and SR group(P<0.001). ClC-1protein expression was positively correlated with left atrial dimension and AFduration [(r=0.368,P=0.002)(r=0.487,P=0.000)].(3)The content of ClC-2mRNA in CAF group(1.26±0.13) was significantly higher than that in SRgroup(1.03±0.14) (P<0.001),There was no significant difference between PAFgroup(1.04±0.15) and SR group(P>0.05). The significant difference was observedbetween PAF and SR group(P<0.01). ClC-2 expression at mRNA level was positivelycorrelated with left atrial dimension and AF duration [(r=0.441,P<0.001)(r=0.331,P=0.005)].The ClC-2 protein expression in CAF group(52.81±5.76)was significantly higher than that in SR group(40.52±7.72)(P<0.001),There wassignificant difference between PAF group(47.21±7.16) and SR group(P<0.05). Thesignificant difference was also observed between PAF and SR group(P<0.05).ClC-2 protein expression was positively correlated with left atrial dimensionand AF duration [(r=0.269,P=0.023)(r=0.430,P=0.000)].(4)The content ofClC-3 mRNA in CAF group(1.07±0.22)was significantly higher than that in SRgroup (0.89±0.21) (P<0.01),and it was significantly correlated with AFduration (r=0.376,P=0.001).There was no significant difference in the geneexpression of ClC-3 between PAF group (0.92±0.23) and SR group (0.89±0.21)although the content of ClC-3 mRNA was slightly higher than that in SR group(P>0.05).The ClC-3 protein expression in CAF group(41.60±7.67) wassignificantly higher than that in SR group(29.35±5.89)(P<0.001),There was nosignificant difference between PAF group(35.16±7.65) and SR group(P=0.05). Thesignificant difference was also observed between PAF and SR group(P<0.05).ClC-3 protein expression was positively correlated with left atrial dimensionand AF duration[(r=0.383,P=0.001)(r=0.384,P=0.001)]. (5) The content of CFTRmRNA in CAF group (1.20±0.12) was significantly higher than that in SR group(1.04±0.12) (P<0.001),There was no significant difference between PAF group(1.08±0.18) and SR group although the content of CFTR mRNA was slightly higherthan that in SR group (P>0.05). The significant difference was observed betweenPAF group and SR group (P<0.05). CFTR expression at mRNA level was positivelycorrelated with left atrial dimension (r=0.312,P=0.008).The CFTR proteinexpression in CAF group(45.44±8.91) was significantly higher than that in SRgroup(30.28±8.41)(P<0.001),There was significant difference between PAFgroup(40.61±4.80) and SR group(P<0.01). There was no difference between PAFand SR group(P>0.05). CFTR protein expression was no correlated with left atrialdimension but positively correlated with AF duration(r=0.373,P=0.001).Conclusions Chloride channels ClC-1,ClC-2,ClC-3 and CFTR do express in humanatrial tissue and the data suggest that increased gene expression of chloridechannels ClC-1,ClC-2,ClC-3 and CFTR may be one of the molecular pathogenesis ofatrial tissue electrical remodeling in patients with atrial fibrillation(AF).