Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level
Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level
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DOI：
10.1161/circgenetics.108.832345
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发表时间：
2009-08-01
影响因子：
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通讯作者：
Tomaselli, Gordon F.
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文献类型：
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作者：
Barth, Andreas S.;Aiba, Takeshi;Tomaselli, Gordon F.
背景-心脏机电不同步导致左心室内工作负荷、耗氧量和心肌灌注的区域差异。我们假设，这种不同步也会诱导心肌转录组的区域特异性改变，这些改变可以通过心脏起搏治疗（CRT）进行纠正。方法和结果-成年犬接受左束分支消融和右心房起搏，200 bpm，持续6周，（不同步心力衰竭，n = 12）或3周，随后以相同的起搏频率进行双心室起搏（CRT，n = 10）。无左束支分支阻滞的对照动物未起搏（n = 13）。在6周时，从左心室（LV）前壁和侧壁分离RNA，并将其杂交到犬特异性44 K微阵列上。超声心动图显示，CRT导致不同步指数显著降低，而不同步心力衰竭和CRT动物的LV功能障碍程度相当。在不同步性心力衰竭中，主要在前LV中观察到基因表达的变化，导致LV内基因表达的区域异质性增加。不同步诱导的1050个转录本的表达变化被CRT逆转至非起搏心脏的水平（假发现率
Background-Cardiac electromechanical dyssynchrony causes regional disparities in workload, oxygen consumption, and myocardial perfusion within the left ventricle. We hypothesized that such dyssynchrony also induces region-specific alterations in the myocardial transcriptome that are corrected by cardiac resynchronization therapy (CRT).Methods and Results-Adult dogs underwent left bundle branch ablation and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, n = 12) or 3 weeks, followed by 3 weeks of resynchronization by biventricular pacing at the same pacing rate (CRT, n = 10). Control animals without left bundle branch block were not paced (n = 13). At 6 weeks, RNA was isolated from the anterior and lateral left ventricular (LV) walls and hybridized onto canine-specific 44K microarrays. Echocardiographically, CRT led to a significant decrease in the dyssynchrony index, while dyssynchronous heart failure and CRT animals had a comparable degree of LV dysfunction. In dyssynchronous heart failure, changes in gene expression were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the LV. Dyssynchrony-induced expression changes in 1050 transcripts were reversed by CRT to levels of nonpaced hearts (false discovery rate