Identification of circular RNAs in cardiac hypertrophy and cardiac fibrosis

Abstract

Cardiac hypertrophy initially serves as an adaptive response to physiological and pathological stimuli. Sustained hypertrophy progress to pathological cardiac hypertrophy, cardiac fibrosis and ultimately lead to heart failure, one of the leading medical causes of mortality worldwide. Intervention of pathological cardiac hypertrophy can effectively reduce the occurrence of heart failure. Abundant factors, such as adrenergic, angiotensin, and endothelin (ET-1) receptors, have been shown to participate in the regulation of pathological cardiac hypertrophy. Recently, an increasing number of studies have indicated that circRNA and circRNA-miRNA–mRNA network regulation is indispensable for the posttranscriptional regulation of mRNA in cardiac hypertrophy. In our study, the morphological, cardiac function and pathological changes during cardiac hypertrophy were investigated. RNA sequencing identified 93 circRNAs that were differentially expressed in the TAC_2w group, and 55 circRNAs in the TAC_4w group compared with the sham group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified several significant pathways, including hypertrophic cardiomyopathy, extracellular matrix (ECM)-receptor interaction and focal adhesion. Coexpression analyses were performed for differentially expressed circRNAs and differentially expressed mRNAs. Based on gene set enrichment analysis (GSEA), 8 circRNAs (mmu-Nfkb1_0001, mmu-Smad4_0007, mmu-Hecw2_0009, mmu-Itgbl1_0002, mmu-Lrrc2_0005, mmu-Cpeb3_0007, mmu-Ryr2_0040, and mmu-Rtn4_0001) involved in cardiac hypertrophy and cardiac fibrosis were identified. We validated some key circRNAs by qPCR. The crucial coexpression of circRNA–mRNA and its interaction with miRNA showed the possible mechanism of circRNAs in the process of cardiac dysfunction. Our results may provide promising targets for the treatment of pathological cardiac hypertrophy and fibrosis.

Identification and validation of pyroptosis-related genes as potential biomarkers for hypertrophic cardiomyopathy: A comprehensive bioinformatics analysis

“…[54] Additionally, ECM-receptor interaction is an essential pathway in cardiac hypertrophy. [55,56] Therefore, we hypothesized that ANXA2 might regulate a potential mechanism that could serve as a therapeutic target for HCM.…”

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling

“…The CPEB3 also involved in synaptic plasticity and spatial memory 27 . Circular RNA, mmu-Cpeb3_0007 was related to cardiac hypertrophy and cardiac fibrosis based on gene set enrichment analysis in mouse model of cardiac hypertrophy 30 . In addition, CPEB3 suppresses EMT by blocking the interaction between colorectal cancer cells and tumor-associated macrophages via decreasing the IL-6/STAT3 signaling 31 .…”

The long noncoding RNA THBS1-AS1 promotes cardiac fibroblast activation in cardiac fibrosis by regulating TGFBR1

“…The heart tissues were routinely dehydrated, paraffin-embedded, and sectioned at 5 μm for H&E staining. H&E staining, Masson’s trichrome staining, and WGA were performed as previously described ( 56 ). To evaluate the degree of cardiac fibrosis, the ratio of blue-stained (collagen) to the total tissue area was assessed using ImageJ software (NIH; 10–12 sections were randomly selected per heart).…”