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Published on: September 15, 2018
Serum microRNA profiles in cats with hypertrophic cardiomyopathy
K Weber1, N Rostert, S Bauersachs
1Faculty of Veterinary Medicine, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Veterinaerstr. 13, 80539, Munich, Germany, karin.weber@lmu.de.
Abstract:
The role of microRNAs (miRNAs) in the pathogenesis of heart diseases of humans and rodents, as well as their diagnostic potential, has recently received much attention, but comparable studies for spontaneous disease models in the domestic cat are missing. Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. The pathology is largely unknown, but is suspected to be influenced by genetic background. In this study, we examined the miRNA profiles in the serum of cats with stable congestive heart failure caused by HCM (n = 11) and healthy control cats (n = 12) using miRNA arrays. 965 out of 2026 miRNAs could be detected in at least six samples of either of the groups. Eleven mammalian miRNAs were differentially expressed between the groups with a fold change ≥ 1.6. Hierarchical cluster analysis resulted in distinct separation of the two groups. After correction for multiple testing (adjusted p < 0.05), a higher expression of miR-381-3p, miR-486-3p, miR-4751, miR-476c-3p, miR-5700, miR-513a-3p, and miR-320e in the HCM group was confirmed. Additionally, miR-1246 was found to be upregulated 3-fold in the HCM group using quantitative RT-PCR. Software analysis of the significantly regulated miRNAs revealed 49 mRNA targets involved in cardiac hypertrophy. Cats with primary HCM show a distinct miRNA profile that includes miRNAs that have already been shown to be differentially regulated in human patients and rodent models for cardiac disease. Studying HCM as a spontaneous cardiac disease of the cat may help to reveal additional pathophysiologic pathways.
Insights
MicroRNAs (miRNAs) show distinct serum profiles in cats with hypertrophic cardiomyopathy (HCM), a common feline heart disease. These findings may offer new diagnostic insights and reveal underlying disease mechanisms.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in human and rodent heart diseases, but their role in feline hypertrophic cardiomyopathy (HCM) is understudied.
- HCM is the most prevalent cardiac condition in domestic cats, with largely unknown pathology potentially linked to genetics.
Purpose of the Study:
- To investigate miRNA profiles in the serum of cats with HCM-induced congestive heart failure.
- To identify differentially expressed miRNAs and their potential mRNA targets in feline HCM.
- To explore the utility of feline HCM as a spontaneous disease model for comparative cardiac research.
Main Methods:
- Serum samples from 11 cats with HCM and 12 healthy controls were analyzed using miRNA arrays.
- Differential expression analysis identified 11 significantly altered miRNAs (fold change ≥ 1.6).
- Quantitative RT-PCR validated the upregulation of miR-1246; bioinformatic analysis predicted 49 mRNA targets involved in cardiac hypertrophy.
Main Results:
- A distinct miRNA profile was observed in cats with HCM compared to healthy controls.
- Eleven miRNAs, including miR-381-3p, miR-486-3p, and miR-1246, were significantly differentially expressed.
- Predicted mRNA targets are associated with pathways involved in cardiac hypertrophy.
Conclusions:
- Feline HCM exhibits a unique serum miRNA signature, with several miRNAs mirroring those found in human and rodent cardiac disease models.
- These findings highlight the potential of studying spontaneous feline HCM to elucidate cardiac disease pathogenesis.
- The identified miRNAs may serve as potential biomarkers for feline cardiac conditions.
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