Mechanisms
Beyond oxidised phospholipids: diacylglycerols, a novel endothelial receptor and accelerated coagulation emerge as new Lp(a) cellular targets, Koschinsky group review finds (Curr Opin Lipidol 2025)
Original title: The complex pro-atherosclerotic role of lipoprotein(a): a multiplicity of cellular targets
This review by Assini, Boffa and Koschinsky surveys recent advances in understanding the specific cellular targets through which Lp(a) drives atherogenesis. Genetic evidence shows Lp(a) is six-fold more atherogenic per particle than LDL, and clinical imaging confirms greater atherosclerotic plaque burden and severity with elevated Lp(a). A novel study in human monocytes identified diacylglycerols and lysophosphatidic acid as pro-inflammatory lipid species carried by Lp(a), acting independently of the already-known oxidised phospholipids, while a newly identified cell-surface receptor on endothelial cells offers another route for Lp(a) uptake into vascular cells. Several studies also point to accelerated coagulation, via Lp(a)'s effects on platelet aggregation and monocyte tissue factor expression, as a further mechanistic target. The authors argue these cell-specific mechanisms will help identify novel therapeutic targets for the many patients with elevated Lp(a) who currently have few treatment options.
Original abstract
Purpose Of Review: Elevated plasma lipoprotein(a) (Lp(a)) is a causal and independent risk factor for atherosclerotic cardiovascular disease; therefore, understanding the fundamental mechanisms underlying Lp(a)-mediated pathogenesis is of significant clinical importance. This review summarizes recent advances in understanding the precise cellular targets of Lp(a) in atherogenesis, uncovering potential therapeutic avenues worth exploring.
Recent Findings: Genetic evidence reveals that Lp(a) is six-fold more atherogenic per particle than LDL, and clinical imaging studies show increased atherosclerotic plaque burden and severity in patients with elevated Lp(a). A novel study using human monocytes uncovered diacylglycerols and lysophosphatidic acid as lipid species that contribute to the pro-inflammatory impacts of Lp(a), independent of the known pro-inflammatory oxidized phospholipids. The identification of a novel cell-surface receptor on endothelial cells involved in Lp(a) uptake offers another exploratory direction in vascular cells involved in atherosclerosis. Several studies have also pointed to accelerated coagulation as a potential target of Lp(a), involving Lp(a)-mediated impacts on platelet aggregation and monocyte tissue factor expression.
Summary: An understanding of these cell-specific targets of Lp(a) in atherogenesis will aid the Lp(a) field in identifying novel therapeutic targets for patients with elevated Lp(a), for whom few available therapeutic strategies currently exist.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.