RNA interactions in right ventricular dysfunction induced type II cardiorenal syndrome

Abstract

Right ventricular (RV) dysfunction induced type II cardiorenal syndrome (CRS) has a high mortality rate, but little attention has been paid to this disease, and its unique molecular characteristics remain unclear. This study aims to investigate the transcriptomic expression profile in this disease and identify key RNA pairs that regulate related molecular signaling networks. We established an RV dysfunction-induced type II CRS mouse model by pulmonary artery constriction (PAC). PAC mice developed severe RV hypertrophy and fibrosis; renal atrophy and dysfunction with elevated creatinine were subsequently observed. Expression profiles in RV and kidney tissues were obtained by whole transcriptome sequencing, revealing a total of 741 and 86 differentially expressed (DE) mRNAs, 159 and 29 DEmiRNAs and 233 and 104 DEcircRNAs between RV and kidney tissue, respectively. Competing endogenous RNA (ceRNA) networks were established. A significant alteration in proliferative, fibrotic and metabolic pathways was found based on GO and KEGG analyses, and the network revealed key ceRNA pairs, such as novel_circ_002631/miR-181a-5p/Creb1 and novel_circ_002631/miR-33-y/Kpan6. These findings indicate that significantly dysregulated pathways in RV dysfunction induced type II CRS include Ras, PI3K/Akt, cGMP-PKG pathways, and thyroid metabolic pathways. These ceRNA pairs can be considered potential targets for the treatment of type II CRS.

Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States

“…Thus, this also serves as an excellent approach for studying TH-mediated effects on the heart (both the ventricles) and also on the kidneys (both right and left). A mouse model of right ventricular hypertrophy and dysfunction following pulmonary artery constriction reported that downregulated pairs of coding/non-coding RNAs were enriched in the TH signaling pathway in cardiac tissues [ 63 ]. However, this is the first study to present a comprehensive outlook of LV cardiac noncoding RNAs and their interactions under altered TH states.…”

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

“…Exosomal circLDLR/miR-1294/CYP19A1 represses estradiol manufacture in PCOS (51). Key ceRNA pairs in metabolic pathways may participate in right ventricular dysfunction (52). circRNA/lncRNA/miRNA/mRNA inhibits macrophage inflammation in type 1 diabetes mellitus (T1DM) (53).…”

miRNAs in Uremic Cardiomyopathy: A Comprehensive Review

“…The impact of a panel of cardio-specific miRNAs on the PPARα signaling, as well as on other intracellular pathways, was further investigated in another experimental model of CKD following chronic heart disease (CHD), also known as type-2 cardio-renal syndrome (CRS) [ 31 ]. Interestingly, in this study, CHD was induced by pulmonary artery constriction (PAC), an experimental model of pulmonary hypertension that ends with the induction of a pathological, dysfunctional remodeling that affects mostly the right ventricle (RV).…”