Lp(a)'s structural resemblance to plasminogen drives both plaque instability and impaired fibrinolysis in myocardial infarction, a narrative review (Rom J Morphol Embryol 2024)

Lipoprotein (a) [Lp(a)] is a recognized independent cardiovascular (CV) risk factor with significant implications in the morphopathology of atherosclerotic plaques, particularly in the context of myocardial infarction (MI). Structurally, Lp(a) consists of a low-density lipoprotein (LDL) particle covalently bound to apolipoprotein A (ApoA), and its resemblance to plasminogen (PLG) underpins its dual proatherogenic and prothrombotic effects. Elevated Lp(a) levels disrupt endothelial repair mechanisms, enhance the deposition of oxidized LDL, and promote foam cell formation, which are critical for the initiation and progression of atherosclerosis. Pathologically, atherosclerotic plaques associated with Lp(a) display hallmark features of instability, including thin fibrous caps, increased macrophage infiltration, calcification, and fragile neovascularization. These features contribute to plaque ruptures and thrombotic complications. Additionally, the structural similarity of Lp(a) to PLG interferes with fibrinolysis, creating a prothrombotic environment that exacerbates the risk of acute ischemic events. Genetic and non-genetic factors influence plasma Lp(a) concentrations, with significant inter-individual and ethnic variability contributing to varying CV risk profiles. Despite advancements in the understanding of the pathophysiological role of Lp(a), effective therapeutic options remain limited. Current management focuses on mitigating traditional CV risk factors, while emerging therapies, such as antisense oligonucleotides and short interfering ribonucleic acid (siRNA) targeting hepatic ApoA production, offer promising avenues for reducing Lp(a) levels. Further clinical validation of these therapies is warranted. This review underscores the importance of incorporating Lp(a) measurement into routine CV risk assessment and emphasizes the need for continued research on its morphopathological impacts and therapeutic modulation, with the aim of reducing the burden of atherosclerosis and MI.