Abstract: PO1014
The Adaptive Response of the Vein to CKD: A Transcriptomics Perspective
Session Information
- Vascular Access Arena: Challenges, Progress, and Prospects
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Vascular Access
Authors
- Martinez, Laisel, University of Miami School of Medicine, Miami, Florida, United States
- Challa, Akshara Sree, University of Miami School of Medicine, Miami, Florida, United States
- Tabbara, Marwan, University of Miami School of Medicine, Miami, Florida, United States
- Rojas, Miguel G., University of Miami School of Medicine, Miami, Florida, United States
- Duque, Juan Camilo, University of Miami School of Medicine, Miami, Florida, United States
- Salman, Loay H., Albany Medical College, Albany, New York, United States
- Vazquez-Padron, Roberto I., University of Miami School of Medicine, Miami, Florida, United States
Background
The impact of CKD on gene expression in the vascular wall remains unknown, particularly in veins, despite their fundamental role as conduits for hemodialysis.
Methods
In this study, we investigated the CKD fingerprint on the transcriptome of basilic veins by analyzing 48 pre-access veins from end-stage renal disease patients and 20 veins from non-CKD trauma donors by bulk RNA sequencing.
Results
We uncovered 16,893 differentially expressed genes (DEG) between CKD and control individuals (log2FoldChange>1, FDR<0.05). The presence of kidney disease caused a noticeable decrease in transcriptional activity in veins, with the downregulation of >97% of DEG transcripts. These included 6,081 non-coding RNAs, 3,826 protein-coding genes, and other miscellaneous transcripts. In contrast, a unique set of 462 genes was upregulated in CKD veins vs. controls, 161 of which corresponded to non-coding RNAs, 201 to protein-coding genes, and the rest to minor RNA biotypes. Gene set enrichment analysis (GSEA) identified a suppression of pathways related to vascular maintenance, cell morphogenesis, cell metabolism, and microtubule-based cytoskeletal functions. Interestingly, the protein-coding genes upregulated in CKD veins belonged to processes related to gas transport and detoxification of oxidative stress byproducts.
Conclusion
In conclusion, we have uncovered a profound suppressive effect of CKD on the venous transcriptome, likely affecting basic cell functions such as metabolism, cell division, and migration. We also identified a transcriptomic signature of upregulated genes in response to oxidative stress which may play a fundamental role in cell survival in the CKD environment.
Funding
- NIDDK Support