Urine proteomics in the diagnosis of stable angina

Abstract

BackgroundWe have previously described a panel of 238 urinary polypeptides specific for established severe coronary artery disease (CAD). Here we studied this polypeptide panel in patients with a wider range of CAD severity.MethodsWe recruited 60 patients who underwent elective coronary angiography for investigation of stable angina. Patients were selected for either having angiographic evidence of CAD or not (NCA) following coronary angiography (n = 30/30; age, 55 ± 6 vs. 56 ± 7 years, P = 0.539) to cover the extremes of the CAD spectrum. A further 66 patients with severe CAD (age, 64 ± 9 years) prior to surgical coronary revascularization were added for correlation studies. The Gensini score was calculated from coronary angiograms as a measure of CAD severity. Urinary proteomic analyses were performed using capillary electrophoresis coupled online to micro time-of-flight mass spectrometry. The urinary polypeptide pattern was classified using a predefined algorithm and resulting in the CAD238 score, which expresses the pattern quantitatively.ResultsIn the whole cohort of patients with CAD (Gensini score 60 [40; 98]) we found a close correlation between Gensini scores and CAD238 (ρ = 0.465, P < 0.001). After adjustment for age (β = 0.144; P = 0.135) the CAD238 score remained a significant predictor of the Gensini score (β =0.418; P < 0.001). In those with less severe CAD (Gensini score 40 [25; 61]), however, we could not detect a difference in CAD238 compared to patients with NCA (−0.487 ± 0.341 vs. −0.612 ± 0.269, P = 0.119).ConclusionsIn conclusion the urinary polypeptide CAD238 score is associated with CAD burden and has potential as a new cardiovascular biomarker.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0246-y) contains supplementary material, which is available to authorized users.

Comparison of Urine and Plasma Peptidome Indicates Selectivity in Renal Peptide Handling

“…This database is regularly updated, currently storing datasets from over 50 000 urine samples (healthy controls and patients with different diseases), encompassing endogenous peptide signals and respective sequence information . Multiple studies have shown that such endogenous urinary peptides combined in classifiers represent powerful tools in the diagnosis and clinical assessment of several diseases such as kidney diseases, different cancers, and cardiovascular diseases . However, less is known about the origin of these peptides.…”

Integrating Genes Affecting Coronary Artery Disease in Functional Networks by Multi-OMICs Approach

“…However, proteome studies are still rare in relation to CAD, mostly due to the complex methodology involved. There have been some investigations in the past few years, aiming at characterizing the proteomes of several CAD-related tissues and cell types, including human arterial smooth muscle cells ( 71 ), platelets ( 72 ), as well as body fluids such as urine ( 73 ).…”

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

“…In cardiovascular disease both approaches have been deployed to lead to a better global understanding of coronary artery disease [27]; or the rapid targeted analysis of the concentrations of angiotensin II (Ang II), Ang-(1–7), Ang III, and Ang IV [28]. In addition it is also possible to analyze native peptides, where no digestive enzyme is used in the preparation, such as the diagnostic biomarkers present in urine for coronary artery disease [29,30]. …”