Three main mechanisms may be involved in the increased cardiovascular risk caused by elevated Lp(a)1
Pro-atherogenic
Oxidised phospholipids (OxPLs) on Lp(a) likely contribute to its pro-inflammatory and pro-atherogenic potential, and pro-osteogenic potential in calcific aortic valve stenosis (CAVS).1-4
- Endothelial cell binding
- Upregulation of adhesion molecules
- Smooth muscle cell proliferation Proteoglycan matrix binding
- Foam cell formation
- Necrotic core formation
- Lesion calcification
Pro-inflammatory
Lp(a) elicits pro-inflammatory responses of vascular and immune cells, which are key
initiating steps in atherosclerosis.1,5-8
- Macrophage Interleukin 8 (IL-8) expression
- Monocyte cytokine release
- Oxidised phospholipids
- Monocyte chemotaxis / transmigration
- Lp(a) carries Monocyte Chemoattractant Protein-1 (MCP-1)
Pro-thrombotic
A pro-thrombotic role for Lp(a) has been hypo-thesised since the discovery of apo(a) sharing extensive homology (75-99%) with the blood clotting protein plasminogen. Potential pro-thrombotic mechanisms of Lp(a) include promotion of platelet aggregation, accelerated coagulation, more resistant fibrin structures and vulnerable plaques.1,4,9,10
- Plasminogen activation
- Fibrin degradation
- Endothelial cell Plasminogen activator inhibitor-1 (PAI-1) expression
- Tissue factor pathway inhibitor (TFPI) activity
- Platelet activation
References: 1. Reyes-Soffer G, et al. Am J Prev Cardiol. 2024;18:100651, 2. Rath M, et al. Arteriosclerosis. 1989;9(5):579–592., 3. van Dijk RA, et al. J Lipid Res. 2012;53(12):2773–2790. 4. Tsimikas S. J Am Coll Cardiol. 2017;69(6):692–711. 5. Tsimikas S, et al. N Engl J Med. 2005;353(1):46–57. 6. Van der Valk FM, et al. Circulation. 2016;134:611–624. 7. Schnitzler JG, et al. Circ Res. 2020;126(10):1346–1359. 8. Stiekema LCA, et al. Eur Heart J. 2020;41(24):2262–2271. 9. Boffa MB & Koschinsky ML. J Lipid Res. 2016;57(5):745–757. 10. Boffa MB. Atherosclerosis. 2022;349:72–81