TY - JOUR
T1 - Unique MicroRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks
AU - Naga Prasad, Sathyamangala V.
AU - Duan, Zong Hui
AU - Gupta, Manveen K.
AU - Surampudi, Venkata Suresh K.
AU - Volinia, Stefano
AU - Calin, George A.
AU - Liu, Chang Gong
AU - Kotwal, Ashwin
AU - Moravec, Christine S.
AU - Starling, Randall C.
AU - Perez, Dianne M.
AU - Sen, Subha
AU - Wu, Qingyu
AU - Plow, Edward F.
AU - Croce, Carlo M.
AU - Karnik, Sadashiva
PY - 2009/10/2
Y1 - 2009/10/2
N2 - It is well established that gene expression patterns are substantially altered in cardiac hypertrophy and heart failure, but the reasons for such differences are not clear. MicroRNAs (miRNAs) are short noncodingRNAsthat provide a novel mechanism for gene regulation. The goal of this study was to comprehensively test for alterations in miRNA expression using human heart failure samples with an aim to build signaling pathway networks using predicted targets for the miRNAs and to identify nodal molecules that control these networks. Genome-wide profiling of miRNAs was performed using custom-designed miRNA microarray followed by validation on an independent set of samples. Eight miRNAs are significantly altered in heart failure of which we have identified two novel miRNAs that are yet to be implicated in cardiac pathophysiology. To gain an unbiased global perspective on regulation by altered miRNAs, predicted targets of eight miRNAs were analyzed using the Ingenuity Pathways Analysis network algorithm to build signaling networks and identify nodal molecules. The majority of nodal molecules identified in our analysis are targets of altered mi-RNA sand are known regulators of cardiovascular signaling. A heart failure gene expression data base was used to analyze changes in expression patterns for these target nodal molecules. Indeed, expression of nodal molecules was altered in heart failure and inversely correlated to miRNA changes validating our analysis. Importantly, using network analysis we have identified a limited number of key functional targets that may regulate expression of the myriad proteins in heart failure and could be potential therapeutic targets.
AB - It is well established that gene expression patterns are substantially altered in cardiac hypertrophy and heart failure, but the reasons for such differences are not clear. MicroRNAs (miRNAs) are short noncodingRNAsthat provide a novel mechanism for gene regulation. The goal of this study was to comprehensively test for alterations in miRNA expression using human heart failure samples with an aim to build signaling pathway networks using predicted targets for the miRNAs and to identify nodal molecules that control these networks. Genome-wide profiling of miRNAs was performed using custom-designed miRNA microarray followed by validation on an independent set of samples. Eight miRNAs are significantly altered in heart failure of which we have identified two novel miRNAs that are yet to be implicated in cardiac pathophysiology. To gain an unbiased global perspective on regulation by altered miRNAs, predicted targets of eight miRNAs were analyzed using the Ingenuity Pathways Analysis network algorithm to build signaling networks and identify nodal molecules. The majority of nodal molecules identified in our analysis are targets of altered mi-RNA sand are known regulators of cardiovascular signaling. A heart failure gene expression data base was used to analyze changes in expression patterns for these target nodal molecules. Indeed, expression of nodal molecules was altered in heart failure and inversely correlated to miRNA changes validating our analysis. Importantly, using network analysis we have identified a limited number of key functional targets that may regulate expression of the myriad proteins in heart failure and could be potential therapeutic targets.
UR - http://www.scopus.com/inward/record.url?scp=70350463883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350463883&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.036541
DO - 10.1074/jbc.M109.036541
M3 - Article
C2 - 19641226
AN - SCOPUS:70350463883
SN - 0021-9258
VL - 284
SP - 27487
EP - 27499
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -