MicroRNA expression analysis: clinical advantage of propranolol reveals key microRNAs in myocardial infarction |
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Authors: | Zhu Wenliang Yang Lei Shan Hongli Zhang Yong Zhou Rui Su Zhe Du Zhimin |
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Institution: | Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. |
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Abstract: | BackgroundAs playing important roles in gene regulation, microRNAs (miRNAs) are
believed as indispensable involvers in the pathogenesis of myocardial
infarction (MI) that causes significant morbidity and mortality. Working on
a hypothesis that modulation of only some key members in the miRNA
superfamily could benefit ischemic heart, we proposed a microarray based
network biology approach to identify them with the recognized clinical
effect of propranolol as a prompt.MethodsA long-term MI model of rat was established in this study. The microarray
technology was applied to determine the global miRNA expression change
intervened by propranolol. Multiple network analyses were sequentially
applied to evaluate the regulatory capacity, efficiency and emphasis of the
miRNAs which dysexpression in MI were significantly reversed by
propranolol.ResultsMicroarray data analysis indicated that long-term propranolol administration
caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed
expression, implying that intentional modulation of miRNA expression might
show favorable effects for ischemic heart. Our network analysis identified
that, among these miRNAs, the prime players in MI were miR-1, miR-29b and
miR-98. Further finding revealed that miR-1 focused on regulation of myocyte
growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation,
respectively.ConclusionOur study illustrates how a combination of microarray technology and
functional protein network analysis can be used to identify disease-related
key miRNAs. |
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