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Published on: August 28, 2018
Proteomic Analysis of Serum Proteins from Patients with Severe Coronary Artery Calcification
BuChun Zhang1, XiangYong Kong1, GuangQuan Qiu1
1Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001 Hefei, Anhui, China.
Insights
This study identified four serum proteins—complement C5, fibrinogen gamma, pyruvate kinase M2, and tropomyosin 4—as potential biomarkers for predicting severe coronary artery calcification (CAC). These findings may aid in early detection and management of cardiovascular disease.
Area of Science:
- Cardiovascular Proteomics
- Biomarker Discovery
- Molecular Diagnostics
Background:
- Coronary artery calcification (CAC) lacks comprehensive proteomic investigation for novel markers.
- This study aimed to compare serum protein expression in patients with and without severe CAC.
Purpose of the Study:
- To identify novel serum protein biomarkers for severe coronary artery calcification (CAC).
- To validate the diagnostic potential of identified proteins in an independent cohort.
Main Methods:
- Data-independent acquisition (DIA)-based proteomics screened serum from 30 severe CAC patients and 30 controls.
- Bioinformatics analyzed differentially expressed proteins and pathways.
- Enzyme-linked immunosorbent assay (ELISA) and ROC curve analysis validated candidate biomarkers.
Main Results:
- 81 proteins were upregulated and 29 downregulated in severe CAC patients (fold change > 1.5, p < 0.05).
- Differentially expressed proteins were linked to complement/coagulation cascades, platelet activation, actin cytoskeleton regulation, and glycolysis.
- Serum levels of complement C5 (C5), fibrinogen gamma (FGG), pyruvate kinase isoform M2 (PKM2), and tropomyosin 4 (TPM4) correlated with CAC severity.
Conclusions:
- Elevated serum C5, FGG, PKM2, and TPM4 levels are associated with severe CAC.
- These proteins show potential as novel biomarkers for predicting coronary calcification.
Background:
Proteomic studies investigating novel molecular markers of coronary artery calcification (CAC) are scarce.This study compared the protein expression in the serum of patients with severe CAC and non-CAC.
Methods:
The serum from 30 patients with severe CAC and 30 matched-controls were screened by data-independent acquisition(DIA)-based proteomic technology. Bioinformatics analysis tools were used to analyze the underlying molecular mechanisms of the differentially expressed proteins. Candidate proteins were further validated by an enzyme-linked immunosorbent assay (ELISA) in an independent cohort. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of the candidate proteins.
Results:
Among the 110 identified proteins, the expression of 81 was significantly upregulated, whereas 29 proteins were downregulated (fold change 1.5; p 0.05) between patients with and without CAC. Bioinformatics analysis indicated that the differential proteins are involved in complement and coagulation cascades, platelet activation, regulation of actin cytoskeleton, or glycolysis/gluconeogenesis pathways. Further verification showed that serum levels of complement C5 (C5), fibrinogen gamma (FGG), pyruvate kinase isoform M2 (PKM2), and tropomyosin 4 (TPM4) were consistent with the proteomic findings, which could allow discrimination between CAC and non-CAC patients.
Conclusions:
This study revealed that high serum levels of serum C5, FGG, PKM2, and TPM4 proteins were linked to severe CAC. These proteins may be developed as biomarkers to predict coronary calcification.
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