| Title: | A Chemokine Profile Linked to Both Triglyceride-Rich Lipoproteins and Lipoprotein(a), But Not LDL, Is Associated With Cardiovascular Disease |
| Journal: | JACC Basic to Translational Science |
| Published: | 13 Oct 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42868980/ |
| DOI: | https://doi.org/10.1016/j.jacbts.2026.101736 |
Publication 21536
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Abstract
Triglyceride-rich lipoproteins (TRL) and lipoprotein(a) [Lp(a)] demonstrate heightened per-particle atherogenicity compared with low-density lipoproteins (LDL), yet mechanistic underpinnings remain unclear. Using Mendelian randomization in >46,000 UK Biobank participants, we linked genetically determined variation in TRL/remnants, LDL, and Lp(a) to 2,920 plasma proteins and found causal associations with 432, 58, and 111 proteins, respectively. Notably, TRL/remnants and Lp(a) both impacted chemokine-signaling and leukocyte-chemotaxis pathways, distinct from LDL's effect on lipid metabolism. A specific chemokine signature linked to both TRL and Lp(a) accounted for around 40% (with wide confidence limits) of the TRL/remnant cholesterol: cardiovascular disease (CVD) association. However, a more general causal relationship between plasma chemokine concentrations and CVD risk independent of a TRL/Lp(a) effect was not supported by quantitative trait loci analysis. These results are compatible with a model in which TRL/Lp(a)-driven chemokine activation contributes meaningfully to CVD risk.</p>
9 Authors
- Elias Björnson
- Martin Adiels
- Jakub Morze
- Florentina Porsch
- Anders Gummesson
- Christoph J Binder
- Clemens Wittenbecher
- Chris J Packard
- Jan Borén
1 Application
| Application ID | Title |
|---|---|
| 82018 | Improved biomarkers of cardiovascular disease |
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