Author + information
Background: Recent evidence suggested beneficial effects of vitamin D receptor activator, paricalcitol (PAR) in experimental heart failure (HF) especially in CKD models. ZSF1 rats are a hybrid transgenic murine model of metabolic syndrome, diabetic nephropathy and HF. We hypothesized that PAR treatment would lead to changes in gene expression that are associated with protective pathways in the heart.
Methods: To test our hypothesis, ZSF1 male rats were treated for 10 weeks with 0.2 μg PAR twice a week with untreated rats as controls and sacrificed at 31 weeks age to harvest the heart. mRNA library was prepared from isolated heart RNA using TruSeq Stranded mRNA Library Kit. Gene expression quantification and transcriptome analysis was performed using Illumina HiSeq 2000. The differential gene list from this analysis was imported into Ingenuity® Pathway Analysis which was used for analysis of data.
Results: PAR had a significant effect on the several genes and pathways. The upregulated canonical pathways include signaling by Rho family, Gα 12, 13, tight junction signaling, thyroxine metabolism, pathways of serotonin and melatonin degradation, xenobiotic metabolism signaling, type 2 diabetes signaling. The upregulated molecules include cadherin 6, cingulin, glucosyltransferase like 1B, UDP glucuronosyltransferase family, solute carrier family 2, Ras association domain family. The down regulated pathways include androgen biosynthesis, STAT 3 pathway, hepatic fibrosis, signaling by Rho family GTPases, non small cell lung cancer signaling, thrombin signaling, epithelial adherence junction signaling, estrogen dependent breast cancer signaling, NFkB signaling, and axonal guidance signaling. The down regulated molecules include epithelial growth factor receptor, chemokine receptor (C-C motif) 5, cytochrome p 450 family 17 subfamily a, TGF alpha, cadherin 3, carbohydrate (N – acetyl glucosamine, SLIT guidance ligand 2 and EGFR.
Conclusions: Gene profiling studies in heart failure showed significant modulation in multiple pathways. The pathogenic significance of these affected genes and signaling pathways need further investigation to get additional insights into PAR effects.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 1:15 p.m.-1:25 p.m.
Session Title: Put Your Codon! Genetic Insights Into Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1226M-09
- 2017 American College of Cardiology Foundation