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Published on: January 28, 2020
TNFR Pathway-Related Proteins and Recurrent Coronary Artery Disease Events
Jiwoo Lee1, Tiffany R Bellomo2, Jennifer L Halford3
1Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Insights
Coronary artery disease (CAD) complications persist despite treatments. This study identified 102 proteins linked to recurrent CAD events, emphasizing tumor necrosis factor receptor (TNFR) pathway involvement.
Area of Science:
- Cardiovascular Research
- Proteomics
- Immunology
Background:
- Coronary artery disease (CAD) remains a leading global cause of mortality.
- Existing treatments and lifestyle modifications do not fully mitigate CAD complications.
- Understanding residual risk factors is crucial for improving patient outcomes.
Purpose of the Study:
- To identify specific proteins and molecular pathways associated with recurrent CAD events.
- To elucidate the underlying mechanisms contributing to residual risk in CAD patients.
- To uncover potential therapeutic targets for managing CAD progression.
Main Methods:
- Utilized UK Biobank data from 1,009 participants with baseline proteomic measures and CAD.
- Employed Olink plasma proteomic analysis to measure 1,463 proteins.
- Applied Cox proportional hazards regression to model associations between proteins and recurrent CAD events.
Main Results:
- 102 out of 1,463 proteins were independently associated with recurrent CAD events.
- Tumor necrosis factor receptor (TNFR) activity was significantly enriched (100-fold enrichment).
- Specific proteins like tumor necrosis factor-alpha, TNFR1, and TNFR2 showed significant associations with increased risk of recurrent CAD.
Conclusions:
- The study highlights the complex role of TNFR1 and TNFR2 pathways in CAD progression.
- Findings suggest inflammation-related targets within the TNFR pathway are critical for therapeutic strategies.
- Further research is needed to translate these proteomic findings into clinical interventions for CAD.
Background:
Despite optimization with lifestyle modifications and medications, complications of coronary artery disease (CAD) remain the leading cause of adult mortality worldwide.
Objectives:
This study aimed to identify proteins and pathways linked to recurrent CAD events to better understand residual risk.
Methods:
We used data from 1,009 participants in the UK Biobank with baseline Olink plasma proteomic measures and CAD. Cox proportional hazards regression modeled the association between proteins measured and recurrent CAD events in follow-up.
Results:
Participants had a mean age of 62.51 years (SD 5.94) at enrollment; 183 (18.14%) were females and 656 (65.01%) had recurrent CAD events over 11.40 (IQR: 8.00-14.69) years of follow-up. 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 = 6.37 × 10-10). Of the 16 proteins related to TNF annotated by the Gene Ontology database, tumor necrosis factor-alpha had a risk estimate of 1.36 (95% CI: 1.17-1.57; P = 6.38 × 10-5), TNFR1 (TNFRSF1A) had a risk estimate of 1.73 (95% CI: 1.43-2.09; P = 1.23 × 10-8), and TNFR2 (TNFRSF1B) had a risk estimate of 1.27 (95% CI: 1.13-1.44; P = 9.15 × 10-5) for recurrent CAD events.
Conclusions:
Although TNFR1 and TNFR2 were initially thought to have opposing roles in cardiac remodeling postmyocardial infarction, 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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