微小RNA与心脏电重构的研究进展(3)
综上所述,miRNA与电重构关系密切,与心律失常的发病机制紧密相关。电重构是心肌电生理特性重塑的过程,心房电重构与房性心律失常(房速、房颤等)关系密切,心室电重构可产生潜在致命室性心律失常(多形性室速、室颤)。认识电重构的细胞与分子机制对于探明潜在治疗靶标十分重要,miRNA介导的离子通道的变化在心肌电重构过程中发挥重要作用,人类中miRNA数量可能高达20 000种,参与30%的人类基因调控,维持心肌细胞正常的电生理网络需要这些miRNA处于动态平衡,一旦平衡被打破,离子通道蛋白表达改变,就会诱发心律失常的发生。因此,miRNA的分子靶向治疗将成为心律失常领域新的研究方向。
参考文献
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, 百拇医药
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, 百拇医药
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, 百拇医药
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, 百拇医药
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, 百拇医药
[13] Lu Y,Zhang Y,Wang N,et al.Control of experimental atrial fibrillation by microRNA-328[J].Circulation,2010,122(23):2378-2387.
[14]王坚刚,孟旭,韩杰,等.非瓣膜性心房颤动相关微小RNA的表达[J].中华医学杂志,2012,92(26):1816-1819.
[15] Carrillo E D,Escobar Y,Gonzrlez G,et a1.Posttranscriptional regulation of the β2-subunit of cardiac L-type Ca2+ channels by MicroRNAs during long-term exposure to isoproterenol in rats[J].J Cardiovasc Pharmacol,201l,58(5):470-478.
, 百拇医药
[16] Yang B,Lin H,Xiao J,et al.The muscle-specific microRNA miR-l regulates cardiac arrhythmogenic potential by targeting GJAl and KCNJ2[J].Nat Med,2007,13(4):486.
[17] Luo X,Lin H,Pan Z,et al.Down-regulation of miR-1/miR-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart[J].J Biol Chem,2008,283(29):
20 045-20 052.
(收稿日期:2015-01-15) (本文编辑:陈丹云), 百拇医药(刘长召 王玲 陈文江 陈灿)
参考文献
[1] Lund E,Guttinger S,Calado A,et al.Nuclear export of microRNA precursors[J].Science,2004,303(5654):95-98.
, 百拇医药
[2] Urakhia M,Tseng Z H.Sudden cardiac death:epidemiology mechanisms and therapy[J].Curr Probl Cardiol,2007,32(9):501-546.
[3] Girmatsion Z,Biliczki P,Bonauer A,et al.Changes in microRNA-1 expression and IKI up-regulation in human atrial fibrillation[J].Heart Rhythm,2009,6(12):1802-1809.
[4] Luo X,Pan Z,Xiao J,et a1.Critical role of microRNAs miR-26 and miR-101 in atrial electrical remodeling in experimental atrial fibrillation[J].J Biol Chem,2010,285(38):29 336-29 347.
, 百拇医药
[5] Du Z,Xu C Q,Slan H,et al.Functional impairment of cardiac transient outward K+ current as a result of abnormally altered cellular environment[J].Clin Exp Pharmacol Physiol,2007,34(3):148-152.
[6] Timofeyev V,He Y,Tuteja D,et al.Cardiac-directed expression of adenylyl cyclase reverses electrical remodeling in cardiomyopathy[J].J Mol Cell Cardiol,2006,41(1):170-181.
[7] Zhao Y,Ransom J F,Li A,et al.Dysregulation of cardiogenesis,cardiac conduction and cell cycle in mice lacking miRNA-l-2[J].Cell,2007,129(2):303.
, 百拇医药
[8] Matkovich S J,Wang W,Tu Y,et a1.MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts[J].Circ Res,2010,106(1):166-175.
[9] Xiao J,Luo X,Lin H,et a1.MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts[J].J Biol Chem,2007,282(17):12 363.
[10]王金华,艾静,王宁,等.高糖对培养乳鼠心肌细胞L型钙通道表达的影响[J].哈尔滨医科大学学报,2006,40(2):96-98.
, 百拇医药
[11] Gellen B,Fernandez-Velasco M,Briec F,et al.Conditional FK-BPl2.6 overexpression in mouse cardiac myocytes pnevents triggered ventricular tachycardia through specific alternations in excitation-contraction coupling [J].Circulation,2008,117(14):1778-1786.
[12] Terentyev D,Belevych A E,Terentyeva R,et al.miR-1 overexpression enhances Ca2+ release and regulatory subunit B56αand causing CaMKII-dependent hyperphosphorylation of RyR2 [J].Cire Res,2009,104(4):514-521.
, 百拇医药
[13] Lu Y,Zhang Y,Wang N,et al.Control of experimental atrial fibrillation by microRNA-328[J].Circulation,2010,122(23):2378-2387.
[14]王坚刚,孟旭,韩杰,等.非瓣膜性心房颤动相关微小RNA的表达[J].中华医学杂志,2012,92(26):1816-1819.
[15] Carrillo E D,Escobar Y,Gonzrlez G,et a1.Posttranscriptional regulation of the β2-subunit of cardiac L-type Ca2+ channels by MicroRNAs during long-term exposure to isoproterenol in rats[J].J Cardiovasc Pharmacol,201l,58(5):470-478.
, 百拇医药
[16] Yang B,Lin H,Xiao J,et al.The muscle-specific microRNA miR-l regulates cardiac arrhythmogenic potential by targeting GJAl and KCNJ2[J].Nat Med,2007,13(4):486.
[17] Luo X,Lin H,Pan Z,et al.Down-regulation of miR-1/miR-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart[J].J Biol Chem,2008,283(29):
20 045-20 052.
(收稿日期:2015-01-15) (本文编辑:陈丹云), 百拇医药(刘长召 王玲 陈文江 陈灿)