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.
Assini et al. (Fri,) studied this question.