PURPOSE: 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. EXPERIMENTAL DESIGN: 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). RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.
PURPOSE: To increase the proteome coverage of humanatherosclerotic plaques and identify low-abundance proteins that may have important functions during the development and progression of atherosclerosis. EXPERIMENTAL DESIGN: 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). RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.
Authors: Sarah J Parker; Lulu Chen; Weston Spivia; Georgia Saylor; Chunhong Mao; Vidya Venkatraman; Ronald J Holewinski; Mitra Mastali; Rakhi Pandey; Grace Athas; Guoqiang Yu; Qin Fu; Dana Troxlair; Richard Vander Heide; David Herrington; Jennifer E Van Eyk; Yue Wang Journal: J Proteome Res Date: 2020-04-07 Impact factor: 4.466
Authors: Song Lin Chua; Joey Kuok Hoong Yam; Piliang Hao; Sunil S Adav; May Margarette Salido; Yang Liu; Michael Givskov; Siu Kwan Sze; Tim Tolker-Nielsen; Liang Yang Journal: Nat Commun Date: 2016-02-19 Impact factor: 14.919
Authors: Ludwig Lautenbacher; Patroklos Samaras; Julian Muller; Andreas Grafberger; Marwin Shraideh; Johannes Rank; Simon T Fuchs; Tobias K Schmidt; Matthew The; Christian Dallago; Holger Wittges; Burkhard Rost; Helmut Krcmar; Bernhard Kuster; Mathias Wilhelm Journal: Nucleic Acids Res Date: 2022-01-07 Impact factor: 16.971