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Review
. 2014 Aug;8(7-8):488-505.
doi: 10.1002/prca.201400014. Epub 2014 Jul 14.

Quantitative proteomics in cardiovascular research: global and targeted strategies

Affiliations
Review

Quantitative proteomics in cardiovascular research: global and targeted strategies

Xiaomeng Shen et al. Proteomics Clin Appl. 2014 Aug.

Abstract

Extensive technical advances in the past decade have substantially expanded quantitative proteomics in cardiovascular research. This has great promise for elucidating the mechanisms of cardiovascular diseases and the discovery of cardiac biomarkers used for diagnosis and treatment evaluation. Global and targeted proteomics are the two major avenues of quantitative proteomics. While global approaches enable unbiased discovery of altered proteins via relative quantification at the proteome level, targeted techniques provide higher sensitivity and accuracy, and are capable of multiplexed absolute quantification in numerous clinical/biological samples. While promising, technical challenges need to be overcome to enable full utilization of these techniques in cardiovascular medicine. Here, we discuss recent advances in quantitative proteomics and summarize applications in cardiovascular research with an emphasis on biomarker discovery and elucidating molecular mechanisms of disease. We propose the integration of global and targeted strategies as a high-throughput pipeline for cardiovascular proteomics. Targeted approaches enable rapid, extensive validation of biomarker candidates discovered by global proteomics. These approaches provide a promising alternative to immunoassays and other low-throughput means currently used for limited validation.

Keywords: Biomarker; Cardiovascular diseases; LC-MS; Mechanism study; Targeted quantification.

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Figures

Figure. 1
Figure. 1. A generic workflow of global quantitative proteomics using a bottom-up (shotgun) approach
Figure. 2
Figure. 2. Label-free quantification strategies
(A) Illustration of the work flow of the ion current-based relative quantification; (B) comparison of the reproducibility of quantitative features by ion current-based vs. spectral count methods for the repetitive analysis of a tissue sample (reproduced from Ref[34]).
Figure. 3
Figure. 3
A high-throughput method development pipeline for sensitive, accurate and reproducible LC/SRM-MS quantification of target proteins in complex matrices, based on an on-the-fly orthogonal array optimization and experimental evaluation. Details can be found in Ref. [136, 137].

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