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Differential gene expression in patients with primary mitral valve disease: identifying potential therapeutic targets in the era of precision medicine
  1. Emily Shih1,
  2. John J Squiers1,
  3. Jacob Turner2,
  4. Michael DiMaio3,
  5. William T Brinkman3,
  6. Robert L Smith3
  1. 1 Surgery, Baylor University Medical Center at Dallas, Dallas, Texas, USA
  2. 2 Baylor Institute for Immunology Research, Dallas, Texas, USA
  3. 3 Cardiothoracic Surgery, Heart Hospital Baylor Plano, Plano, Texas, USA
  1. Correspondence to Dr Emily Shih, Surgery, Baylor University Medical Center at Dallas, Dallas, TX 75246-2088, USA; emily.shih{at}bswhealth.org

Abstract

Primary (degenerative) mitral valve (MV) disease is a result of structural remodeling due to degenerative and adaptive changes of MV tissue. We hypothesized that in patients with primary MV disease undergoing surgery for severe mitral regurgitation (MR), a distinct genetic expression profile within the MV leaflet tissue could be identified as compared with patients without MV disease. Tissue samples from the MV leaflets of 65 patients undergoing MV surgery for MR due to primary MV disease and 4 control cadavers without MV disease were collected and analyzed. MicroRNA transcripts were hybridized to Illumina HumanHT-12 v4 Beadchips. Ingenuity pathway analyses (IPAs) were conducted to provide biological interpretation. Of the approximately 20 000 genes examined, 4092 (20%) were differentially expressed between patients with primary MV disease and normal controls (false discovery rate<0.05). The differentially expressed genes could be clustered into five regulator effect networks from the Ingenuity Knowledge IPA database with a consistency score of >6. These five networks have been previously implicated in pathophysiological cardiac abnormalities, including inhibited contractility of the heart and fatty acid oxidation as well as activation of apoptosis of smooth muscle cells, cardiac degeneration, and hypertrophy of cardiac cells. MV tissue in patients with primary MV disease demonstrated distinct genetic expression patterns as compared with normal controls. Further studies are necessary to determine whether the molecular pathways identified in this experiment may represent potential therapeutic targets to prevent degeneration of MV tissue leading to severe MR.

  • microarray analysis
  • heart valve diseases

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Footnotes

  • Presented at This data were previously presented as an oral presentation at the American Association for Thoracic Surgery Mitral Conclave.

  • Contributors All listed authors made significant contributions to the manuscript that meet the four criteria widely used by the International Committee of Medical Journal Editors to determine authorship. Specifically, ES and JJS helped to design the study, collect and analyze data, and drafted and revised the manuscript. JT performed key data analysis and interpretation, as well as revised the manuscript. MD, WTB, and RLS each assisted with data collection and analysis, study design, and revisions of the manuscript. All authors provided final approval and agreed to be accountable for all aspects of the work.

  • Funding This research was supported in part by a grant from the Cardiovascular Research Review Committee of the Baylor Foundation.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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