| Background Atrial fibrillation (AF) is one kind of the most common clinical arrhythmia, which can easily lead to stroke and heart failure. In addition to age, hypertension, coronary heart disease and thyroid dysfunction, the factor which has more closely relationship with AF is valvular heart disease (VHD), whose share in all patients with AF is12.9%. Calcineurin is a unique calcium/calmodulin (Ca+/CaM) activated protein serine/threonine phosphatase, which is composed of catalytic A subunit (CnA) of60kDa and a regulatory B subunit (CnB) of19kDa. Nuclear factor of activated T cell (NFAT), which is regulated by Ca2+and CaN, is one cytokine produced by T cell when it is stimulated by antigen. Resting phosphorylated NFAT mainly locates in the cytoplasm. After activated, it is dephosphorylated and enters in nucleus, then causing a serious of pathological effects. The role of CaN-NFAT pathway in the pathogenesis of cardiac hypertrophy in recent years has been paid more attention. Cardiac structural remodeling is also an important factor in starting and maintaining AF. Relationship between CaN-NFAT pathway and AF has not been determined. This study aims to investigate the relationship between gene expression of CaN and NFAT and AF.Objective This study attempted to investigate the relationship between CaN-NFAT pathway and AF in patients with VHD.Methods43patients with VHD who underwent valve replacement surgery from March to December were enrolled of2013. They were53.63±8.26year old on average and there were22men and21women. Blood samples and right atrial appendages were taken from24patients with chronic persistent AF and from19patients with sinus rhythm (SR). We also chose20blood samples from healthy individuals as control. Transcription of α-and β-isoforms of CaN subunit A (CnA) and NFATc3, NFATc4in peripheral lymphocytes and right atrial appendages were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR), with β-actin as an internal reference. At the same time, we collected patients’clinical data and various of laboratory findings.Results①RT-PCR detecting expression of mRNA:in comparison with the data in patients with SR and the healthy controls, the mRNA level of CnA a-isoform (0.0211±0.0199vs0.0030±0.0020vs0.0026±0.0019), CnA β-isoform (0.0131±0.0093vs0.0022±0.0018vs0.0031±0.0028) and NFATc3(0.0092±0.0047vs0.0015±0.0011vs0.0019±0.0012) were also elevated in peripheral lymphocytes from patients with AF (P<0.05), and there were no diferences between patients with SR and the healthy controls (P>0.05). In comparison with the data in patients with SR, the mRNA level of CnA a-isoform (0.0117±0.0070vs0.0043±0.0029), CnA β-isoform (0.0661±0.0553vs0.0132±0.0088), NFATc3(0.0105±0.0103vs0.0013±0.0006) and NFATc4(0.0019±0.0013vs0.0010±0.0007) were elevated in cardiac tissues from patients with AF(P<0.05).②Comparison among clinical data: in comparison with the data in patients with SR, the level of BNP and angiotensin Ⅱ were higher and the diameter of left atrium were longer (P<0.05).③NFATc4mRNA level in cardiac tissues was positively correlated with plasma level of angiotensin Ⅱ (r=0.31, P<0.05)Conclusion calcineurin-nuclear factor of activated T cell pathway is associated with AF in patients with VHD. |
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