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Clinical Trial
. 2016 Jun 28:6:28042.
doi: 10.1038/srep28042.

Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

Trayambak Basak  1   2 , Vinay Singh Tanwar  1 , Gourav Bhardwaj  1 , Nitin Bhardwaj  1 , Shadab Ahmad  1 , Gaurav Garg  1 , Sreenivas V  3 , Ganesan Karthikeyan  4 , Sandeep Seth  4 , Shantanu Sengupta  1   2
Affiliations
Clinical Trial

Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

Trayambak Basak et al. Sci Rep. .

Abstract

Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD.

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Figures

Figure 1
Figure 1. Schematic workflow for the iTRAQ based discovery phase analysis.
Figure 2
Figure 2. Significantly (p < 0.0001) differentially expressed protein levels after logistic regression analysis.
Figure 3
Figure 3. A ROC curve showing area under the curve 0.8734 for CAD cases.
See this image and copyright information in PMC

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