| Title: | Large-scale identification of protein biomarkers and therapeutic targets in heart and brain disease |
| Journal: | Nature Cardiovascular Research |
| Published: | 2 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41927926/ |
| DOI: | https://doi.org/10.1038/s44161-026-00799-2 |
Publication 18113
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Abstract
Neurological complications frequently impact morbidity, mortality and quality of life in patients with cardiovascular disease, yet the biological mediators connecting cardiovascular and neurological disease are poorly understood. Here we leverage data from 53,014 individuals with plasma proteomic profiles and 50,228 with cardiac and brain magnetic resonance imaging from the UK Biobank to identify circulating proteins correlated with imaging-derived phenotypes (IDPs); 404 and 76 proteins were associated with cardiac or brain IDPs, and 37 with both. Expression analyses suggested these proteins largely originate from fibroblasts, smooth muscle cells, and macrophages in the arterial vasculature. Pathway analyses highlighted cytokine and vasculature-related processes for cardiac IDPs-associated proteins and extracellular matrix pathways in brain IDPs-associated proteins. Mendelian randomization and genetic colocalization supported causal roles for over 63% of these proteins in disease pathogenesis. Over 90% of the proposed candidates have not previously been established as clinical biomarkers or therapeutic targets and represent a catalog for further research.</p>
15 Keywords
- Biological Specimen Banks
- Biomarkers
- Blood Proteins
- Brain Diseases
- Female
- Heart Diseases
- Humans
- Magnetic Resonance Imaging
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Phenotype
- Predictive Value of Tests
- Proteome
- Proteomics
13 Authors
- Chao Wu
- Dantong Li
- Sumeet A. Khetarpal
- Zixun Yuan
- Shengyuan Huang
- Justin Ralph Baldovino Guerra
- Chunyu Li
- Qiulian Zhou
- Meixi Quan
- Jiaqi He
- Meng Wang
- Huiying Liang
- Anthony Rosenzweig
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