In:
Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-2-4)
Abstract:
Proteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms. Aim We aimed to prospectively screen the proteome of four types of individuals: with or without coronary artery disease (CAD), each with or without multiple risk factors. Associations with individual risk factors and circulating biomarkers were also tested to provide a functional context to the protein hits. Materials and Methods The CAPIRE study ( ClinicalTrials.gov Identifier: NCT02157662) is a cross-sectional study aimed at identifying possible new mechanisms promoting or protecting against atherothrombosis. Quantification (by aptamer technology), ranking (using partial least squares), and correlations (by multivariate regression) of ~5000 plasma proteins were performed in consecutive individuals aged 45–75 years, without previous cardiovascular disease, undergoing computed tomography angiography for suspected CAD, showing either & gt;5/16 atherosclerotic segments (CAD + ) or completely clean arteries (CAD − ) and either ≤ 1 risk factor (RF + ) or ≥3 risk factors (RF − ) (based on history, blood pressure, glycemia, lipids, and smoking). Results Of 544 individuals, 39% were atypical (93 CAD + /RF − ; 120 CAD − /RF + ) and 61% typical (102 CAD + /RF + ; 229 CAD − /RF − ). In the comparison with CAD + /RF − adjusted for sex and age, CAD − /RF + was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUC ROC 's of 0.72–0.81 (overall p = 1.0e −38 ). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA 1c , and smoking. Conclusions In a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA 1c . These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.
Type of Medium:
Online Resource
ISSN:
2297-055X
DOI:
10.3389/fcvm.2021.790289
DOI:
10.3389/fcvm.2021.790289.s001
DOI:
10.3389/fcvm.2021.790289.s002
DOI:
10.3389/fcvm.2021.790289.s003
DOI:
10.3389/fcvm.2021.790289.s004
DOI:
10.3389/fcvm.2021.790289.s005
DOI:
10.3389/fcvm.2021.790289.s006
DOI:
10.3389/fcvm.2021.790289.s007
DOI:
10.3389/fcvm.2021.790289.s008
DOI:
10.3389/fcvm.2021.790289.s009
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2781496-8
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