Related Experiment Video
Updated: May 6, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of
Francisco Javier Munguia-Galaviz1,2, Yanet Karina Gutierrez-Mercado3, Alejandra Guillermina Miranda-Diaz1
1Departamento de Fisiologia, CUCS, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Insights
Chronic kidney disease (CKD) causes early cardiac transcriptional changes, including mitochondrial dysfunction and vimentin upregulation, contributing to cardiorenal syndrome type 4 development.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Molecular Biology
Background:
- Cardiorenal syndrome (CRS) type 4 is common in chronic kidney disease (CKD) patients, often leading to cardiovascular death.
- Early cardiac transcriptional changes in CKD remain poorly understood.
Purpose of the Study:
- To investigate early cardiac transcriptional alterations in a murine model of CKD.
- To identify molecular pathways involved in cardiac remodeling during CKD progression.
Main Methods:
- Utilized a unilateral ureteral obstruction (UUO) mouse model to induce kidney injury.
- Performed histological analysis, RT-qPCR, RNA-sequencing, and bioinformatics to assess cardiac and renal changes at 21 days post-surgery.
Main Results:
- UUO induced significant kidney injury, uremia, and cardiac remodeling with increased collagen and alpha-smooth muscle actin 2.
- RNA-seq identified 76 differentially expressed genes in UUO hearts, enriched in cell cycle, immune response, and oxidative stress pathways.
- Mitochondrial oxidative bioenergetics, autophagy, and peroxisomal pathways were downregulated; vimentin was upregulated.
Conclusions:
- CKD triggers extensive cardiac transcriptional changes, including mitochondrial dysfunction and vimentin upregulation.
- These alterations are crucial in the development of cardiorenal syndrome type 4.
- Homeostasis deregulation and altered fatty-acid metabolism are implicated in CRS type 4 pathogenesis.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
More Related Videos
Related Concept Videos
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:25Chronic Kidney Disease I: Introduction
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Chronic Kidney Disease III: Interprofessional Care
01:18Chronic Kidney Disease IV: Nursing Management