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Genome-wide sequencing and quantification of circulating microRNAs for dogs with congestive heart failure secondary to myxomatous mitral valve degeneration

SeungWoo Jung DVM, PhD1 and Amy Bohan MS2
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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Abstract

OBJECTIVE To characterize expression profiles of circulating microRNAs via genome-wide sequencing for dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve degeneration (MMVD).

ANIMALS 9 healthy client-owned dogs and 8 age-matched client-owned dogs with CHF secondary to MMVD.

PROCEDURES Blood samples were collected before administering cardiac medications for the management of CHF. Isolated microRNAs from plasma were classified into microRNA libraries and subjected to next-generation sequencing (NGS) for genome-wide sequencing analysis and quantification of circulating microRNAs. Quantitative reverse transcription PCR (qRT-PCR) assays were used to validate expression profiles of differentially expressed circulating microRNAs identified from NGS analysis of dogs with CHF.

RESULTS 326 microRNAs were identified with NGS analysis. Hierarchical analysis revealed distinct expression patterns of circulating microRNAs between healthy dogs and dogs with CHF. Results of qRT-PCR assays confirmed upregulation of 4 microRNAs (miR-133, miR-1, miR-let-7e, and miR-125) and downregulation of 4 selected microRNAs (miR-30c, miR-128, miR-142, and miR-423). Results of qRT-PCR assays were highly correlated with NGS data and supported the specificity of circulating microRNA expression profiles in dogs with CHF secondary to MMVD.

CONCLUSIONS AND CLINICAL RELEVANCE These results suggested that circulating microRNA expression patterns were unique and could serve as molecular biomarkers of CHF in dogs with MMVD.

Supplementary Materials

    • Supplementary Figure S1 (PDF 205 kb)
    • Supplementary Figure S2 (PDF 160 kb)
    • Supplementary Figure S3 (PDF 1152 kb)
    • Supplementary Table S1 (PDF 570 kb)
    • Supplementary Table S2 (PDF 620 kb)

Contributor Notes

Address correspondence to Dr. Jung (szj0026@auburn.edu).