Lipoprotein(a), Endothelial Dysfunction and Cardiovascular Disease

Lipoprotein(a) (Lp(a)) is a particle similar to low-density lipoprotein cholesterol and is associated with apolipoprotein (A). High Lp(a) levels are a genetic, independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Endothelial cells, which form the continuous lining of the cardiovascular system, are crucial for vascular function and represent the primary target of Lp(a)-mediated injury. Lp(a) penetrates the endothelial barrier and undergoes oxidative modification, triggering endothelial dysfunction, which is characterized by inflammation, oxidative stress and impaired nitric oxide bioavailability. These disruptions promote monocyte recruitment, foam cell formation and atherosclerosis development. Currently, various drugs that can reduce Lp(a) levels are also involved in regulating endothelial cell function, ultimately reducing the risk of ASCVD. However, the molecular mechanisms underlying Lp(a)-mediated endothelial injury and the extent to which Lp(a) lowering improves endothelial function remain incompletely defined. Clarifying these issues may inform cardiovascular risk stratification and the clinical development of Lp(a)-targeted therapies. This review seeks to consolidate the understanding of the link between Lp(a) levels and endothelial dysfunction, highlighting its pivotal role in cardiovascular disease progression.