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Differential Proteo...
Differential Proteomics of Cardiovascular Risk and Coronary Artery Disease in Humans
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Ferrannini, E (författare)
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Manca, ML (författare)
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- Ferrannini, G (författare)
- Karolinska Institutet
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Andreotti, F (författare)
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Andreini, D (författare)
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Latini, R (författare)
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Magnoni, M (författare)
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Williams, SA (författare)
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Maseri, A (författare)
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Maggioni, AP (författare)
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(creator_code:org_t)
- 2022-02-04
- 2022
- Engelska.
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Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 8, s. 790289-
- Relaterad länk:
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https://www.frontier...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- Proteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms.AimWe 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 MethodsThe 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 >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).ResultsOf 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 AUCROC'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 HbA1c, and smoking.ConclusionsIn 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 HbA1c. These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.
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Till lärosätets databas
- Av författaren/redakt...
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Ferrannini, E
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Manca, ML
-
Ferrannini, G
-
Andreotti, F
-
Andreini, D
-
Latini, R
-
visa fler...
-
Magnoni, M
-
Williams, SA
-
Maseri, A
-
Maggioni, AP
-
visa färre...
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Frontiers in car ...
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Karolinska Institutet