Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics
Abstract
1. Introduction
2. Results
2.1. Proteome Screening for Causal Proteins in CAS
2.2. Causal Proteins for Cardiovascular Disease
2.3. Bayesian Colocalization and Reverse MR for the Causal Relationship Between Causal Proteins and CAS
2.4. Replication Validation for Identified Proteins
2.5. Single-Cell RNA-Seq Differential Expression Analysis for Coronary Plaque Samples and Healthy Vasculature
2.6. Protein–Protein Interaction (PPI) Network, Enrichment Analysis, and Drug Repurposing
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Proteomic Data Source
4.3. GWAS Summary Statistics for Atherosclerosis and Cardiovascular Diseases
4.4. Proteome-Wide MR Analysis for Identifying Causal Proteins
4.5. Bayesian Colocalization Analysis
4.6. Single-Cell RNA-Seq Differential Expression Analysis
4.7. Protein–Protein Interaction, Enrichment Analysis, and Druggability Assessment
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Protein | UniProt | OR (95% CI) | Pdiscovery | Preplication a | Preverse | Colocalization b PPH4 | Panel | Tier |
---|---|---|---|---|---|---|---|---|
PCSK9 | Q8NBP7 | 1.28 (1.22–1.34) | 1.61 × 10−25 | 5.64 × 10−5 | 0.64 | 0.999/0.999 | Cardiometabolic | 1 |
CELSR2 | Q9HCU4 | 0.82 (0.79–0.86) | 3.88 × 10−21 | 1.70 × 10−29 | 0.04 | 0.997/0.994 | Inflammation | 1 |
APOE | P02649 | 0.94 (0.92–0.95) | 2.70 × 10−11 | 1.44 × 10−21 | 0.95 | 0.000/0.000 | Inflammation | 2 |
LPA | P08519 | 1.14 (1.09–1.2) | 5.51 × 10−9 | 4.11 × 10−90 | 0.45 | 0.000/0.000 | Inflammation | 2 |
IL6R | P08887 | 0.96 (0.95–0.98) | 7.77 × 10−8 | 2.05 × 10−5 | 0.78 | 0.986/0.972 | Cardiometabolic | 1 |
FN1 | P02751 | 0.9 (0.86–0.94) | 3.22 × 10−7 | 3.47 × 10−8 | 0.53 | 0.972/0.945 | Inflammation | 1 |
APOA5 | Q6Q788 | 1.06 (1.03–1.09) | 2.17 × 10−6 | 1.62 × 10−4 | 0.44 | 0.000/0.000 | Cardiometabolic | 2 |
AGER | Q15109 | 0.91 (0.87–0.94) | 2.58 × 10−6 | 0.12 | 0.64 | 0.020/0.009 | Inflammation | 3 |
CD4 | P01730 | 0.9 (0.86–0.94) | 5.33 × 10−6 | 0.71 | 0.12 | 0.983/0.966 | Inflammation | 3 |
TGFB1 | P01137 | 1.16 (1.09–1.23) | 5.56 × 10−6 | 2.77 × 10−6 | 0.62 | 0.450/0.290 | Inflammation | 2 |
SPARCL1 | Q14515 | 0.94 (0.91–0.97) | 1.05 × 10−5 | 5.08 × 10−3 | 0.37 | 0.963/0.929 | Cardiometabolic | 1 |
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Wang, H.; Xie, F.; Wang, M.; Ji, J.; Song, Y.; Dai, Y.; Wang, L.; Kang, Z.; Cao, L. Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics. Int. J. Mol. Sci. 2025, 26, 6201. https://doi.org/10.3390/ijms26136201
Wang H, Xie F, Wang M, Ji J, Song Y, Dai Y, Wang L, Kang Z, Cao L. Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics. International Journal of Molecular Sciences. 2025; 26(13):6201. https://doi.org/10.3390/ijms26136201
Chicago/Turabian StyleWang, Hesong, Fengzhe Xie, Meng Wang, Jianxin Ji, Yongzhen Song, Yanyan Dai, Liuying Wang, Zheng Kang, and Lei Cao. 2025. "Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics" International Journal of Molecular Sciences 26, no. 13: 6201. https://doi.org/10.3390/ijms26136201
APA StyleWang, H., Xie, F., Wang, M., Ji, J., Song, Y., Dai, Y., Wang, L., Kang, Z., & Cao, L. (2025). Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics. International Journal of Molecular Sciences, 26(13), 6201. https://doi.org/10.3390/ijms26136201