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TNFR Pathway-Related Proteins and Recurrent Coronary Artery Disease Events
Insights
Identifying proteins linked to recurrent coronary artery disease (CAD) events is crucial for understanding residual risk. This study found 102 proteins, particularly those in the tumor necrosis factor receptor pathway, associated with increased CAD event risk.
Area of Science:
- Cardiovascular Disease Research
- Proteomics
- Inflammation Biology
Background:
- Coronary artery disease (CAD) complications are a leading global cause of mortality.
- Despite current treatments, residual risk for recurrent CAD events persists.
- Understanding the molecular basis of residual risk is essential for improved patient outcomes.
Purpose of the Study:
- To identify novel protein biomarkers associated with recurrent CAD events.
- To elucidate molecular pathways contributing to residual risk in CAD patients.
- To investigate the role of tumor necrosis factor receptor (TNFR) signaling in CAD recurrence.
Main Methods:
- Utilized plasma proteomic data from 1,009 UK Biobank participants with established CAD.
- Analyzed 1,463 proteins for independent associations with recurrent CAD events.
- Applied Gene Ontology enrichment analysis to identify significantly associated molecular functions and pathways.
Main Results:
- 102 proteins were independently associated with recurrent CAD events.
- Tumor necrosis factor receptor (TNFR) activity was significantly enriched (100-fold) among associated molecular functions.
- TNF-alpha, TNFR1, and TNFR2 were all significantly linked to an increased risk of recurrent CAD events.
Conclusions:
- Specific proteins, particularly within the TNFR pathway, are strongly associated with recurrent CAD events.
- The findings highlight the complex role of TNFR1 and TNFR2 in CAD, challenging previous assumptions.
- Identifying inflammation-related targets within these pathways may offer new therapeutic strategies for reducing residual CAD risk.
Abstract:
Despite optimization with lifestyle modifications and medications, complications of coronary artery disease (CAD) remain the leading cause of adult mortality worldwide. This study aimed to identify proteins and pathways linked to recurrent CAD events to better understand residual risk. We used data from 1,009 participants in the UK Biobank (UKB) with baseline Olink plasma proteomic measures and CAD. Among 1,463 proteins tested, 102 proteins were independently associated with recurrent CAD events. Molecular functions were significantly enriched for tumor necrosis factor receptor (TNFR) activity by 100-fold (p-value = 6.37×10 -10 ). Of the 16 proteins related to TNF annotated by Gene Ontology, TNF-alpha, TNFR1, and TNFR2 were all significantly associated with increased risk of recurrent CAD events. While TNFR1 and TNFR2 were initially thought to have opposing roles in cardiac remodeling post-MI, this study highlights the complex interaction between these pathways and the need to identify specific inflammation-related targets to therapeutic strategies.
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