Three TF Gene Co-expression Modules are involved in Pressure-Overload Cardiac Hypertrophy in Male Mice (microRNA). Mus musculus

Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes. Overall design: In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. Eight-week-old adult male mice (C57BL/6J) were anaesthetized and subjected to pressure overload by transverse aortic banding (TAB). The RNAs of cardiac tissues were taken from Sham- and TAB-operated mice at 3, 5, 7, 14, and 28 days after surgery. Then, the expression changes of mRNAs and miRNAs were estimated by cDNA and miRNA microarrays, respectively.