Abstract 17203: Identification of Angiopoietin 2 as a Novel Biomarker for Acute Aortic Dissection by Trancriptome Study
Background: Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to discover the potential AAD biomarkers using a transcriptomic strategy.
Methods: Ascending aortic tissue was collected from eight male patients with Stanford Type A aortic dissection (mean age, 48.1±4.9 years) and eight healthy male organ donors (mean age, 47.9±6.7 years). Array based genome-wide gene expression profiling were performed on a panel of aortic tissues from 4 AAD patients and 4 controls. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR). The plasma levels of potential biomarker were determined in 20 AAD patients (mean age, 53.3±13.5 years; male, 14/20) and 18 controls (mean age, 51.9±11.2 years; male, 13/18) by enzyme linked immunosorbent assay.
Results: Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (FDR-adjusted p<0.01, foldchange>3.0). The significantly upregulated gene set was highly enriched among functional categories involved in Toll-like receptor signaling pathway and ECM-receptor interaction (p<0.001). By using literature data (Gene Ontology, UniProt, and Human Plasma Proteome), we identified two proteins (angiopoietin 2 (ANGPT2), chemokine (C-C motif) ligand 3 (CCL3)) as candidate biomarkers for blood-based detection of AAD. The qRT-PCR assay demonstrated that ANGPT2 and CCL3 increased 2.4-fold (P<0.01) and 3.6-fold (P=0.02) in the entire patient group, respectively. Furthermore, although the plasma concentrations of CCL3 were unchanged, ANGPT2 levels were significantly 1.9-fold higher in AAD patients than in controls (P=0.001). The ROC analysis indicated that ANGPT2 had reasonable accuracy for diagnosis of AAD (the area under curves, 0.81; 95% CI, 0.67-0.95; P=0.001).
Conclusions: Our preliminary study offers the first evidence that ANGPT2 is associated with AAD and could be a promising biomarker for detection of AAD. Future studies with a larger sample size of normal and AAD patient samples should be pursued.
- © 2013 by American Heart Association, Inc.