Recent Developments in Clinical Plasma Proteomics—Applied to Cardiovascular Research

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.

High-Multiplex Aptamer-Based Serum Proteomics to Identify Candidate Serum Biomarkers of Oral Squamous Cell Carcinoma

“…Thus, the discovery of suitable disease biomarkers has long been hampered by the complexity and a huge dynamic range of serum/plasma protein concentrations across more than 12 logs combined with the lack of proteomic technologies to measure large numbers of proteins across such a broad dynamic range. Recent achievements in technologies addressed these limitations to specify and quantify the human plasma and serum proteome and improve biomarker development [ 17 , 20 , 23 ]. Among these, 2-gel electrophoresis (2DE) coupled with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF), as well as two-dimension liquid chromatography in combination with tandem mass spectrometry, were considered as state-of-the-art for almost a decade in discovery proteomics.…”

“…Among these, 2-gel electrophoresis (2DE) coupled with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF), as well as two-dimension liquid chromatography in combination with tandem mass spectrometry, were considered as state-of-the-art for almost a decade in discovery proteomics. However, the application of affinity-based, high multiplex methods such as the here-used aptamer-based SOMAscan, or the proximity extension assay (PEA, Olink), technologies are being applied increasingly with great success to an ever increasing number of clinically relevant studies [ 17 , 18 , 20 , 21 , 22 , 23 , 26 , 33 ]. So far, the SOMAscan technology has been linked to the biomarker discovery of various chronic and acute diseases [ 22 , 24 , 25 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…Only recently, highly exact, unbiased, affinity-based methods for high scale proteome analysis with high sensitivity and specificity for a broad range of proteins across the entire dynamic range in complex fluids such as serum of plasma were introduced that overcame the shortcomings of conventional, even advanced, mass spectrometry technologies to detect novel biomarkers of disease [ 17 , 18 ]. The SOMAscan technology was introduced in 2012 for quantitative proteome analysis.…”

Correlation Between Cardiac Index, Plasma Troponin I, Myocardial Histopathology, CPB and AoX Duration in Glutamine versus No Glutamine Administered Patients with Low Ejection Fraction Undergoing Elective On-Pump CABG Surgery: Secondary Analysis of an RCT

“…In predicting outcomes of CABG surgeries, protein biomarkers are used, in this instance, the troponin I is proposed as a biomarker of choice after cardiac surgery. 9 , 10 Cardiac troponin I is a preferred biomarker in detecting myocardial necrosis and diagnosing myocardial infarction 11 , 12 Another assessment tool in detecting myocardial injury is through histopathological examination. Cardiac myocyte apoptosis during cardiac surgery could be analysed based on the detection of DNA breaks by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL).…”

The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights

“…Therefore, the proteome seems highly relevant to characterize a biological system [ 9 ]. Proteomics hold great potential for new insights into pathogenesis related to the continuing presence of a ductus arteriosus and possible novel biomarkers for diagnostic, prognostic, and monitoring purposes in preterm neonates [ 10 ].…”