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Published on: January 28, 2020
Data-independent acquisition proteomics reveals circulating biomarkers of coronary chronic total occlusion in humans
Jun Li1,2,3, Xue-Jun Jiang1,2,3, Qun-Hui Wang4,5
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Insights
This study identified seven key proteins in plasma that change during coronary chronic total occlusion (CTO) progression and after treatment. These proteins, including CSF1 and LGALS1, may offer new therapeutic targets for preventing CTO.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Biomarker Discovery
Background:
- The pathophysiology of coronary chronic total occlusion (CTO) remains incompletely understood.
- Identifying plasma biomarkers is crucial for understanding CTO progression and treatment response.
Purpose of the Study:
- To investigate plasma proteomic profiles in patients with CTO.
- To identify protein dynamics associated with CTO progression and immediate post-revascularization.
- To discover potential plasma biomarkers for CTO.
Main Methods:
- Quantitative proteomics (data-independent acquisition) was used to analyze plasma samples from controls and CTO patients (pre- and post-percutaneous coronary intervention).
- Enzyme-linked immunosorbent assay (ELISA) was employed to validate differentially expressed proteins (DEPs).
- Gene ontology (GO) and protein-protein interaction (PPI) analyses were performed on identified DEPs.
Main Results:
- Proteomics identified 69 DEPs in CTO patients compared to controls, enriched in pathways like negative regulation of proteolysis and lipid location.
- 43 DEPs were identified in CTO vessels post-revascularization compared to pre-PCI, enriched in extracellular structure organization and fibrinolysis.
- Seven proteins (ADH4, CSF1, galectin, LPL, IGF2, IgH, LGALS1) showed dynamic alterations, with CSF1 and LGALS1 validated by ELISA.
Conclusions:
- The study reveals dynamic molecular responses in plasma following CTO reperfusion.
- Seven specific proteins were identified as potential therapeutic targets for preventing coronary CTO.
- These findings contribute to a better understanding of CTO pathophysiology and potential treatment strategies.
Introduction:
The pathophysiology of coronary chronic total occlusion (CTO) has not been fully elucidated.
Methods:
In the present study, we aimed to investigate the potential plasma biomarkers associated with the pathophysiologic progression of CTO and identify protein dynamics in the plasma of CTO vessels immediately after successful revascularization. We quantitatively analyzed the plasma proteome profiles of controls (CON, n = 10) and patients with CTO pre- and post- percutaneous coronary intervention (PCI) (CTO, n = 10) by data-independent acquisition proteomics. We performed enzyme-linked immunosorbent assay (ELISA) to further confirm the common DEPs in the two-group comparisons (CON vs. CTO and CTO vs. CTO-PCI).
Results:
A total of 1936 proteins with 69 differentially expressed proteins (DEPs) were detected in the plasma of patients with CTO through quantitative proteomics analysis. For all these DEPs, gene ontology (GO) analysis and protein-protein interaction (PPI) analysis were performed. The results showed that most of the proteins were related to the negative regulation of proteolysis, regulation of peptidase activity, negative regulation of hydrolase activity, humoral immune response, and lipid location. Furthermore, we identified 1927 proteins with 43 DEPs in the plasma of patients with CTO vessels after immediately successful revascularization compared to pre-PCI. GO analysis revealed that the above DEPs were enriched in the biological processes of extracellular structure organization, protein activation cascade, negative regulation of response to external stimulus, plasminogen activation, and fibrinolysis. More importantly, we generated a Venn diagram to identify the common DEPs in the two-group comparisons. Seven proteins, ADH4, CSF1, galectin, LPL, IGF2, IgH, and LGALS1, were found to be dynamically altered in plasma during the pathophysiological progression of CTO vessels and following successful revascularization, moreover, CSF1 and LGALS1 were validated via ELISA.
Conclusions:
The results of this study reveal a dynamic pattern of the molecular response after CTO vessel immediate reperfusion, and identified seven proteins which would be the potential targets for novel therapeutic strategies to prevent coronary CTO.
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