RNA Sequencing of Cardiac in a Rat Model Uncovers Potential Target LncRNA of Diabetic Cardiomyopathy

Abstract

Background: Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients; however, its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) are involved in the development of various cardiovascular diseases, but little is known in DCM.Objective: The present study was conducted to investigate the altered expression signature of lncRNAs and mRNAs by RNA-sequencing and uncovers the potential targets of DCM.Methods: A DCM rat model was established, and the genome-wide expression profile of cardiac lncRNAs and mRNAs was investigated in the rat model with and without DCM by RNA-sequencing. Bioinformatics analysis included the co-expression, competitive endogenous RNA (ceRNA) network, and functional enrichment analysis of deregulated lncRNAs and mRNAs.Results: A total of 355 lncRNA transcripts and 828 mRNA transcripts were aberrantly expressed. The ceRNA network showed that lncRNA XR_351927.3, ENSRNOT00000089581, XR_597359.2, XR_591602.2, and XR_001842089.1 are associated with the greatest number of differentially expressed mRNAs and AURKB, MELK, and CDK1 may be the potential regulatory targets of these lncRNAs. Functional analysis showed that these five lncRNAs are closely associated with fibration, cell proliferation, and energy metabolism of cardiac myocytes, indicating that these core lncRNAs have high significance in DCM.Conclusions: The present study profiled the DCM-specific lncRNAs and mRNAs, constructed the lncRNA-related ceRNA regulatory network, and identified the potential prognostic biomarkers, which provided new insights into the pathogenesis of DCM.

Multi-omics insights into potential mechanism of SGLT2 inhibitors cardiovascular benefit in diabetic cardiomyopathy

“…In this present study, we established the T1DM rat model by intraperitoneal injection of STZ and treatment with EMPA for 12 weeks to investigate changes in proteins and metabolites in the myocardium. The animal experiment results confirmed that diabetes contributed to a pronounced DCM characterized by mitochondrial dysfunction, impaired lipid metabolism, myocardial fibrosis, and associated diastolic and systolic functional impairments of the heart, which were consistent with the observations in previous studies ( 21 , 29 ). Dysregulation of metabolism increased production of AGEs and apoptosis, inflammation, and impaired calcium were all suggested to explain the cardiac impairment in DCM ( 30 ).…”

“…The mitochondrial structure was further examined by standard transmission electron microscopy (TEM) in the laboratory of Guangzhou Huiyuanyuan Pharmaceutical Technology Co., LTD. Fresh myocardium sample preparation for TEM was performed as previously described ( 21 ).…”

Comparison of the negative effect of remimazolam and propofol on cardiac contractility: Analysis of a randomised parallel‐group trial and a preclinical ex vivo study

“…We then analysed the expression patterns of cardiac GABA A receptor subunits using RNA sequence data collected from rat 9 and human hearts. 10 Focusing on α, β and γ subunits, which consist of propofol and benzodiazepine binding sites (α-β subunit interface for propofol 12 and α-γ subunit interface for benzodiazepine 13,14 ), interestingly, none of the genes for γ subunits (GABRG1, GABRG2 and GABRG3) were detectable despite the presence of α and β subunits in both rat and human hearts (Figure 4A,B), while all these subunits are highly expressed in neuronal cells of the human brain (Figure S2).…”

“…Additionally, in a clinical study, the effects of remimazolam on cardiac contractility and other haemodynamic parameters were compared with those of propofol during the induction of general anaesthesia. Finally, because propofol and remimazolam bind to different binding sites of GABA A receptors consisting of different subunits, the expression pattern of the subunits of GABA A receptor in the hearts was assessed using previous RNA sequence data in both rats 9 and humans. 10,11 2 | RESULTS 2.1 | Remimazolam does not possess a direct negative effect on cardiac contractility as opposed to propofol: A preclinical ex vivo study using isolated rat hearts…”

Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart

“…Chronic hyperglycemia is associated with fibrosis-driven myocardial stiffness, cardiomyocyte hypertrophy, and altered substrate metabolism triggering structural and functional impairment in the cardiac tissue leading to DCM [ 2 – 5 ]. Glucose-induced progression of these cardiac pathologies is mediated through aberrant activation of the signaling pathways that are persuaded by changes in the cardiac transcriptome [ 6 , 7 ]. The underlying molecular mechanisms involved in this transcriptional reprogramming are poorly understood.…”