心房颤动患者离子重构的分子基础

Molecular basis of ionic remodeling in patients with atrial fibrillation

目的 研究心房颤动 (AF)患者离子重构的分子基础。方法 以先天性心脏病 (CHD)和风湿性心脏病 (RHD)持续窦性心律 (SR)患者为对照 ,应用半定量RT PCR法检测RHD伴阵发性AF(PAF)慢性AF 6个月 (AF 6M )和慢性AF >6个月 (AF >6M )患者心房肌L 型电压依赖钙通道α1c亚基 (LVDCCα1c)、电压依赖KV4 3钾通道α亚基 (VDKV4 3α)和电压依赖钠通道α亚基 (VDSCα)mRNA的表达。结果 SR组内CHD患者与RHD患者LVDCCα1c、VDKV4 3α和VDSCα的mRNA表达差别无明显性 ;与对照组相比 ,各组AF患者VDSCα的表达没有改变 ;LVDCCα1c在AF >6M患者中的表达显著下降 ,而在PAF和AF 6M患者中的表达有不同程度下调 ,但无统计学意义 ;LVDCCα1cmRNA表达与心房率、左、右心房内径成明显负相关 ,并且其表达随AF分数增高逐渐下降 ;单因素协方差分析 (ANOVA)矫正心房内径的影响 ,AF >6M患者α1cmRNA表达仍明显下降 (P <0 0 1)。KV4 3αmRNA在PAF、AF 6M和AF >6M患者中的表达均显著降低。KV4 3钾通道α亚单位mRNA表达与AF分数、左心房内径和平均心房率均成明显负相关 ,经ANOVA剔除左心房内径的影响 ,各组mRNA表达较SR组仍显著下降 (P <0 0 5 )。结论 L 型钙通道和KV4 3钾通道转录水平下调是相应ICaL和Ito1重构的分子基础 。

Objective The purpose of this study is to investigate the molecular basis of ionic remodeling in patients with atrial fibrillation (AF). Methods The mRNA expression of L-type voltage dependent calcium channel α1c subunit (LVDCC α1c)? voltage dependent KV4.3 potassium channel α subunit (VDKV4.3 α) and voltage dependent sodium channel α subunit (VDSC α) were detected by semi-quantitative RT-PCR in patients with paroxysmal atrial fibrillation (PAF), in patients with chronic AF for less than 6 months (AF6 M) and more than 6 months (AF>6 M). Subjects with persisting sinus rhythm (SR) were considered as control group, they all had underlying rheumatic heart disease (RHD) or congenital heart disease (CHD). Semi-quantitative analysis of gene express of above mentioned each channel subunit was performed by imagemaster VDS-CL. Results There were no significant difference in the gene expression of LVDCC α1c? VDSC α and VDKV4.3 α between RHD and CHD patients in SR group; gene expression of VDSC α remained unchanged in all groups. The expression of LVDCC α1c was significantly decreased in patients with AF>6 M and remained stable in patients with PAF and AF6 M. The expression of VDKV4.3 α was reduced significantly in patients with PAF, AF6 M and AF>6 M, as compared with that in patients with sinus rhythm. A significant correlation was found between the mRNA expression of LVDCC α and AF score, mean atrial rate, left and right atrial diameter. One-way ANOVA showed that mRNA expression of LVDCC α1c in AF>6 M was still low after correcting the effect of atrial diameter ( P <0.01). There was a similar significant correlation between mRNA expression of VDKV4.3 α and AF score, left atrial diameter and mean atrial rate. The mRNA expression of KV4.3 α was decreased significantly after the effect of atrial diameter corrected by one-way ANOVA ( P <0.05). Conclusion These data suggest that transcriptional down-regulation of L-type calcium channel and KV4.3 potassium channel may serve as the molecular basis of I CaL and I tol remodeling respectively in patients with chronic AF. The mRNA expression of LVDCC α1c remains unchanged in patients with PAF and AF6 M, whose I CaL remodeling may be associated with post-transcriptional abnormality and/or activation of proteolytic system. The mRNA expression of VDSC α, in accordance with I Na , keep stable in patients with AF.