钙激活氯通道在风心病和先心病患者心脏的表达
首发时间:2015-08-17
摘要:目的 TMEM16A编码的钙激活氯通道(CaCC)在心血管系统中发挥着重要的作用。本课题组曾报道TMEM16A编码的钙激活氯通道参与构成小鼠心脏动作电位1期复极,然而其在人类心脏中表达、功能在病理性重构中的作用还未见报道。方法 本实验采用逆转录PCR(RT-PCR)技术检测先天性心脏病及风湿性心脏病患者心脏组织中TMEM16,Bestrophin家族基因的表达谱;应用荧光定量PCR(qRT-PCR)技术检测TMEM16A基因表达变化情况。结果 RT-PCR结果表明风心病和先心病患者TMEM16家族表达谱存在差异:风心病患者心脏表达除TMEM16D、TMEM16J以外的其他TMEM16成员;而先心病患者心脏仅表达TMEM16A、TMEM16G、TMEM16E及TMEM16K。先心病和风心病患者心脏Bestrophin家族表达谱无差异,都表达Bestrophin2和Bestrophin4。qRT-PCR结果显示,风心病患者心肌组织TMEM16A mRNA 表达量显著高于其在先心病患者心肌组织表达。结论 TMEM16家族表达谱在风湿性心脏病和先天性心脏病中存在差异,并且可编码CaCC的重要基因TMEM16A mRNA 的表达量也存在差异,提示TMEM16A及其家族成员可能参与人类心脏疾病的发生与发展。
关键词: 钙激活氯通道 TMEM16 表达 风湿性心脏病 先天性心脏病
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Expression of calcium-activated chloride channel in congenital heart disease and rheumatic heart disease
Abstract:Objective Calcium-activated chloride channel (CaCC) encoded by TMEM16A plays inportant roles in cardiovascular system. Our previous study has demonstrated that TMEM16A ICl.Ca contributes to the phase 1 repolarization of mouse ventricular action potential duration (APD). However its expression, function in the pathological changes of the human heart has remained unclear. To investigate its potential role in human heart disease, the expression of TMEM16 and Bestrophin family members were primarily investigated in heart tissue from patients with congenital heart disease (CHD) and rheumatic heart disease (RHD). Methods RT-PCR technique was performed to determine the expression profile of TMEM16 and Bestrophin family expression, and quantitative realtime PCR (qRT-PCR) was used to detect the relative mRNA expression level of TMEM16A in human heart tissue. Results RT-PCR results demonstrated that the TMEM16 family member profile was differrent between CHD and RHD: except TMEM16D and TMEM16J, all the members of TMEM16 family were expressed in heart tissue from patients with CHD; but only TMEM16A, TMEM16G, TMEM16E and TMEM16K were expressed in heart tissue from patients with RHD. However, another potential candidate gene for CaCC, Bestrophin did not show expression profile difference between these two heart diseases: Bestrophin2 and Bestrophin4 were expressed in heart tissue from patients with CHD and RHD. qRT-PCR results demonstrated that the expression level of TMEM16A mRNA was significantly up-regulated in the heart tissue from patients with RHD than those from patient with CHD. Conclusion TMEM16 expression profile is different between RHD and CHD. Most importantly, the mRNA amout of TMEM16A which can encode CaCC is differentially expressed between these two heart diseases. Together, these results indicate that TMEM16A and other differentially expressed TMEM16 family member may participate in the development of human heart disease.
Keywords: Calcium activated chloride channel TMEM16 expression Rheumatic heart disease Congenital heart disease
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