Deep proteomic profiling of human carotid atherosclerotic plaques using multidimensional LC‐MS/MS. Issue 7 (2nd July 2014)

• Record Type: Journal Article
• Authors: Hao, Piliang; Ren, Yan; Pasterkamp, Gerard; Moll, Frans L.; de Kleijn, Dominique P. V.; Sze, Siu Kwan; Ge, Ying; Van Eyk, Jennifer
• Is Part Of: Proteomics. Volume 8:Issue 7/8(2014)
• Page Start: 631
• Page End: 635
• Publication Date: 2014-07-02
• Subjects: Proteomics -- Periodicals; 572.605
• DOI: 10.1002/prca.201400007
• Languages: English
• ISSNs: 1862-8346

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="prca1548-sec-0010" sec-type="section"> <title>Purpose</title> <p>To increase the proteome coverage of human atherosclerotic plaques and identify low‐abundance proteins that may have important functions during the development and progression of atherosclerosis.</p> </sec> <sec id="prca1548-sec-0020" sec-type="section"> <title>Experimental design</title> <p>Thirty‐eight human carotid atherosclerotic plaques were pooled into two samples and analyzed in triplicate using offline multidimensional LC‐MS/MS. The collected fractions of trypsin‐digested peptides from Electrostatic Repulsion‐Hydrophilic Interaction Chromatography (ERLIC) were analyzed by LC‐MS/MS on a Q Exactive (Thermo Fisher, MA, USA).</p> </sec> <sec id="prca1548-sec-0030" sec-type="section"> <title>Results</title> <p>A total of 4702 proteins were identified from atherosclerotic plaques at a false discovery rate (FDR) of 1%, of which 3846 were identified with at least 2 unique peptides. Many pathways related to the development and progression of atherosclerosis were identified, such as atherosclerosis signaling, toll receptor signaling pathway and inhibition of matrix metalloproteases. Many low‐abundance proteins with important functions in atherosclerosis that were previously unidentifiable using mass spectrometry based proteomics methods, such as TGF‐β, interleukins and other growth factors, were identified confidently from plaques.</p> </sec> <sec id="prca1548-sec-0040" sec-type="section"> <title>Conclusions and clinical relevance</title> <p>This study has substantially increased the coverage of the atherosclerotic plaque proteome which represents a leap forward in understanding of plaque composition, development and progression. The identification of many low‐abundance proteins may also facilitate biomarker discovery.</p> </sec> </abstract>