Danger-recognizing proteins, β-defensin-128 and histatin-3, as potential biomarkers of recurrent coronary events.

Abstract

Conventional risk factors have limited ability to predict recurrent events in subjects with first-time coronary artery disease(CAD). This aim of this study was to identify novel biomarkers using comparative global proteome analysis to improve the risk assessment for recurrent coronary events. We used samples from phase-I of the Indian Atherosclerosis Research Study(IARS), consisting of 2,332subjects, of whom 772were CAD-affected subjects, including 152with recurrent events identified during a 5-year follow-up period. Global proteome analysis was performed on serum samples of 85subjects with recurrent coronary events and 85age- and gender-matched subjects with first-time CAD using surface-enhanced laser desorption ionization time-of-flight mass spectrometry with CM10 arrays. TagIdent was used for protein identification followed by validation by western blot analysis and ELISA. Data were analyzed by logistic analysis, Cox-regression, hazards ratio, C-statistics and combined-marker risk score using SPSS version-17 and R-package version-2.13.0 software. We identified 16significantly differentially expressed protein peaks. Of these, 2peaks corresponding to m/z8588 and1864 were identified as β-defensin-128 and histatin-3, belonging to the danger-recognizing peptide family, which exhibited a significant independent association with recurrent events(odds ratios of7.49 and1.4, respectively). C-statistics improved significantly from 0.677 for conventional risk factors alone to 0.800(p-value=0.001) in combination with β-defensin-128 and histatin-3 with a hazards ratio of1.833. A combined risk score of β-defensin-128 and histatin-3 could reclassify 112out of the 170subjects into intermediate- and high-risk groups. On the whole, our data indicate that β-defensin-128 and histatin-3 may be potential biomarkers whch may be used to improve risk the stratification for recurrent coronary events.