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- W2003480595 abstract "Apoptosis is a hallmark of multiple etiologies of heart failure, including dilated cardiomyopathy. Since microRNAs are master regulators of cardiac development and key effectors of intracellular signaling, they represent novel candidates for understanding the mechanisms driving the increased dysfunction and loss of cardiomyocytes during cardiovascular disease progression. To determine the role of cardiac miRNAs in the apoptotic response, we used microarray technology to monitor miRNA levels in a validated murine phospholambam mutant model of dilated cardiomyopathy. 24 miRNAs were found to be differentially expressed, most of which have not been previously linked to dilated cardiomyopathy. We showed that individual silencing of 7 out of 8 significantly down-regulated miRNAs (mir-1, -29c, -30c, -30d, -149, -486, -499) led to a strong apoptotic phenotype in cell culture, suggesting they repress pro-apoptotic factors. To identify putative miRNA targets most likely relevant to cell death, we computationally integrated transcriptomic, proteomic and functional annotation data. We showed the dependency of prioritized target abundance on miRNA expression using RNA interference and quantitative mass spectrometry. We concluded that down regulation of key pro-survival miRNAs causes up-regulation of apoptotic signaling effectors that contribute to cardiac cell loss, potentially leading to system decompensation and heart failure." @default.
- W2003480595 created "2016-06-24" @default.
- W2003480595 creator A5010789029 @default.
- W2003480595 creator A5026206371 @default.
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- W2003480595 creator A5060081041 @default.
- W2003480595 creator A5061039656 @default.
- W2003480595 creator A5072404345 @default.
- W2003480595 creator A5076978787 @default.
- W2003480595 date "2015-01-01" @default.
- W2003480595 modified "2023-09-26" @default.
- W2003480595 title "Systems analysis reveals down-regulation of a network of pro-survival miRNAs drives the apoptotic response in dilated cardiomyopathy" @default.
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