Circulating "LncPPARδ" From Monocytes as a Novel Biomarker for Coronary Artery Diseases

Medicine (Baltimore). 2016 Feb;95(6):e2360. doi: 10.1097/MD.0000000000002360.

Abstract

To investigate long noncoding RNA NONHSAT112178 (LncPPARδ) as a biomarker for coronary artery disease (CAD) in peripheral blood monocyte cells, RT-qPCR was performed to validate the microarray results, receiver operating characteristic curve was applied to study the potential of LncPPARδ as a biomarker. Diagnostic models from LncPPARδ alone or combination of risk factors were constructed by Fisher criteria. The expression of genes neighboring the LncPPARδ gene was examined with RT-qPCR in THP-1 cell line treated with LncPPARδ siRNA. Using a diagnostic model by Fisher criteria, the consideration of risk factors increased the optimal sensitivity from 70.00% to 82.00% and decreased the specificity from 94.00% to 78.00%. The consideration of risk factors also increased area under the receiver operating characteristic curve from 0.727 to 0.785 (P = 0.001), from 0.712 to 0.768 (P = 0.01), and from 0.769 to 0.835 (P = 0.07), in the original, training, and test sets, respectively. Finally, we found that the expression of peroxisome proliferator-activated receptor δ (PPARδ), Adipose Differentiation-Related Protein (ADRP), and Angiopoietin-like 4 (ANGPTL4) were affected by LncPPARδ silencing.Our present study indicated that LncPPARδ, especially combined with risk factors, can be a good biomarker for CAD. LncPPARδ regulates the expression of neighboring protein-coding genes, PPARδ and its direct target genes ADRP and ANGPTL4.

Trial registration: ClinicalTrials.gov NCT01629225.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Case-Control Studies
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • PPAR delta / genetics*
  • RNA, Long Noncoding / blood*
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers
  • PPAR delta
  • RNA, Long Noncoding

Associated data

  • ClinicalTrials.gov/NCT01629225