RNA interactions in right ventricular dysfunction induced type II cardiorenal syndrome

Area of Science:

• Cardiovascular and Renal Medicine
• Molecular Biology
• Genomics

Background:

• Type II cardiorenal syndrome (CRS), driven by right ventricular (RV) dysfunction, has a high mortality rate.
• The molecular underpinnings and specific RNA regulatory networks in RV dysfunction-induced type II CRS remain poorly understood.
• Investigating these molecular characteristics is crucial for developing effective treatments.

Purpose of the Study:

• To elucidate the transcriptomic expression profile in RV dysfunction-induced type II CRS.
• To identify key RNA pairs, specifically competing endogenous RNA (ceRNA) networks, that regulate molecular signaling pathways.
• To uncover potential therapeutic targets for type II CRS.

Main Methods:

• Establishment of a mouse model for RV dysfunction-induced type II CRS using pulmonary artery constriction (PAC).
• Whole transcriptome sequencing of RV and kidney tissues to identify differentially expressed mRNAs, miRNAs, and circRNAs.
• Bioinformatic analysis, including Gene Ontology (GO) and KEGG pathway analyses, to construct ceRNA networks.

Main Results:

• PAC mice exhibited severe RV hypertrophy, fibrosis, renal atrophy, and dysfunction.
• Significant differential expression of mRNAs, miRNAs, and circRNAs was observed in both RV and kidney tissues.
• Identified key ceRNA pairs, such as novel_circ_002631/miR-181a-5p/Creb1 and novel_circ_002631/miR-33-y/Kpan6.
• Dysregulated pathways included Ras, PI3K/Akt, cGMP-PKG, and thyroid metabolic pathways.

Conclusions:

• RV dysfunction-induced type II CRS involves significant alterations in proliferative, fibrotic, and metabolic pathways.
• The identified ceRNA networks and dysregulated pathways provide novel insights into the molecular mechanisms of type II CRS.
• Key ceRNA pairs represent promising therapeutic targets for managing type II CRS.