Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support.
Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support.
复制标题
DOI：
10.1161/circulationaha.108.813576
复制
发表时间：
2009-03-10
期刊：
影响因子：
37.8
通讯作者：
Dorn GW 2nd
中科院分区：
文献类型：
--
作者：
Matkovich SJ;Van Booven DJ;Youker KA;Torre-Amione G;Diwan A;Eschenbacher WH;Dorn LE;Watson MA;Margulies KB;Dorn GW 2nd
Much has been learned about transcriptional control of cardiac gene expression in clinical and experimental congestive heart failure (CHF), but less is known about dynamic regulation of microRNAs (miRs) in CHF and during CHF treatment. We performed comprehensive microarray profiling of both miRs and mRNAs in myocardial specimens from human CHF with (n=10) or without (n=17) biomechanical support with left ventricular assist devices (LVAD), in comparison to non-failing hearts (n=11). Twenty-eight miRs were upregulated >2.0-fold (P<0.001) in CHF, with nearly complete normalization of the heart failure miR signature by LVAD treatment. In contrast, of 444 mRNAs that were altered by >1.3-fold in failing hearts, only 29 mRNAs normalized by as much as 25% in post-LVAD hearts. Unsupervised hierarchical clustering of upregulated miRs and mRNAs with nearest centroid analysis and leave-one-out cross validation revealed that combining the miR and mRNA signatures increased the ability of RNA profiling to serve as a clinical biomarker of diagnostic group and functional class. These results show that miRs are more sensitive than mRNAs to the acute functional status of end-stage heart failure, consistent with important functions for regulated miRs in the myocardial response to stress. Combined miR and mRNA profiling may have superior potential as a diagnostic and prognostic test in end-stage cardiomyopathy.
