Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of Cardiorenal syndrome type 4

• Published in: Heliyon Vol. 10; no. 6; p. e27468
• Main Authors: Munguia-Galaviz, Francisco Javier, Gutierrez-Mercado, Yanet Karina, Miranda-Diaz, Alejandra Guillermina, Portilla de Buen, Eliseo, Flores-Soto, Mario Eduardo, Echavarria, Raquel
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 30.03.2024; Elsevier
• Subjects: Cardiorenal; CKD; Heart; Kidney; mRNA; Transcriptomics; Uropathy; Heart; Transcriptomics; mRNA; Cardiorenal; CKD; Kidney; Uropathy
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e27468

Cardiorenal syndrome (CRS) type 4 is prevalent among the chronic kidney disease (CKD) population, with many patients dying from cardiovascular complications. However, limited data regarding cardiac transcriptional changes induced early by CKD is available. We used a murine unilateral ureteral obstruction (UUO) model to evaluate renal damage, cardiac remodeling, and transcriptional regulation at 21 days post-surgery through histological analysis, RT-qPCR, RNA-seq, and bioinformatics. UUO leads to significant kidney injury, low uremia, and pathological cardiac remodeling, evidenced by increased collagen deposition and smooth muscle alpha-actin 2 expression. RNA-seq analysis identified 76 differentially expressed genes (DEGs) in UUO hearts. Upregulated DEGs were significantly enriched in cell cycle and cell division pathways, immune responses, cardiac repair, inflammation, proliferation, oxidative stress, and apoptosis. Gene Set Enrichment Analysis further revealed mitochondrial oxidative bioenergetic pathways, autophagy, and peroxisomal pathways are downregulated in UUO hearts. Vimentin was also identified as an UUO-upregulated transcript. Our results emphasize the relevance of extensive transcriptional changes, mitochondrial dysfunction, homeostasis deregulation, fatty-acid metabolism alterations, and vimentin upregulation in CRS type 4 development. [Display omitted] •UUO is a useful model to study pathological cardiac remodeling in early CKD.•Extensive cardiac transcriptional changes occur in response to UUO.•Upregulated genes are enriched in cell cycle and cardiac repair pathways.•Autophagic, mitochondrial, and peroxisomal pathways are downregulated in UUO hearts.•Mitochondrial dysfunction and vimentin upregulation participate in CRS type 4.