Abstract

The human plasma proteome mirrors the physiological state of the cardiovascular system, a fact that has been used to analyze plasma biomarkers in routine analysis for the diagnosis and monitoring of cardiovascular diseases for decades. These biomarkers address, however, only a very limited subset of cardiovascular diseases, such as acute myocardial infarct or acute deep vein thrombosis, and clinical plasma biomarkers for the diagnosis and stratification cardiovascular diseases that are growing in incidence, such as heart failure and abdominal aortic aneurysm, do not exist and are urgently needed. The discovery of novel biomarkers in plasma has been hindered by the complexity of the human plasma proteome that again transforms into an extreme analytical complexity when it comes to the discovery of novel plasma biomarkers. This complexity is, however, addressed by recent achievements in technologies for analyzing the human plasma proteome, thereby facilitating the possibility for novel biomarker discoveries. The aims of this article is to provide an overview of the recent achievements in technologies for proteomic analysis of the human plasma proteome and their applications in cardiovascular medicine.

Highlights

  • There has been a rise in the use of proteomic approaches for the study of bodily fluids to uncover disease mechanisms that are associated with the cardiovascular system and to improve diagnosis, prognosis, and monitoring in cardiovascular diseases (CVD)

  • Complementing the information that was obtained from traditional risk factors with measurements of the relevant biomarkers in body fluids, the individualized risk stratification and diagnosis of CVD may lead the way for improved patient classification [5]

  • Label-free quantification extracts the MS1 peptide precursor ion chromatogram and uses either the intensity of the highest point or integrates the peak area over the chromatographic time scale [63] as a quantitative measure. Another way of label-free-quantification is spectral counting in which the number peptide spectrum matches (PSMs) from identified unique peptides from a given protein are summed as the number of PSMs that have been shown to correlate with the protein quantity [64]

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Summary

Introduction

There has been a rise in the use of proteomic approaches for the study of bodily fluids to uncover disease mechanisms that are associated with the cardiovascular system and to improve diagnosis, prognosis, and monitoring in cardiovascular diseases (CVD). High-performance biomarkers for CVD stratification, diagnosis of acute myocardial infarct (AMI), heart failure (HF), and other cardiovascular conditions, such as abdominal aortic aneurysms are urgently needed. The plasma proteome contains thousands of proteins and the general assumption is that most of them remain unexplored for their relation to multiple diseases including CVDs. a systematic exploration of all proteins that are present in plasma holds great potential for displaying novel biomarkers for diagnostic, prognostic, and monitoring purposes. Complementing the information that was obtained from traditional risk factors with measurements of the relevant biomarkers in body fluids, the individualized risk stratification and diagnosis of CVD may lead the way for improved patient classification [5]. The current trends within alleviating analytical limitations are explored along with innovative proteomic technologies that are utilized in cardiovascular research that may improve clinical protein biomarker studies in the future

The Human Plasma Proteome and Its Complexity
Cardiovascular Diseases and Related Biomarkers
Preanalytical Steps in Mass Spectrometry-Based Plasma Proteomics
MS-Based Proteomics
Quantitative MS-Based Proteomics
Affinity-Based Proteomics Methods
Aptamer Microarrays (SomaScan)
Proximity Extension Assays (Olink)
Microbead-Based Multiplex Immunoassay (xMAP)
The publicly available
Recent Developments in Plasma Proteomics of Cardiovascular Diseases
Findings
Conclusive Remarks and Outlook
Full Text
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