Mechanisms
Low Lp(a) aids clot dissolution but oxidised Lp(a) blocks it, a biphasic effect mechanistic study finds, explaining Lp(a)'s prothrombotic potential (J Lipid Atheroscler 2025)
Original title: Investigation of the Influence of Lipoprotein(a) and Oxidized Lipoprotein(a) on Plasminogen Activation and Fibrinolysis
This mechanistic study used chromogenic substrate assays and fibrin clots generated from fibrinogen and thrombin to compare how unoxidised versus chemically oxidised Lp(a) affect tissue-plasminogen-activator-triggered plasminogen activation and fibrinolysis, across low and high concentrations of each. Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, consistent with a physiological role, but at higher concentrations, oxidised Lp(a) significantly inhibited plasminogen activation, causing earlier plateauing and reduced overall plasmin generation compared with unoxidised Lp(a). The authors attribute oxidised Lp(a)'s inhibitory effect to its structural similarity to plasminogen and its higher oxidised phospholipid content, which competes with plasminogen for fibrin binding and further impairs fibrinolysis alongside tPA. They conclude that while low Lp(a) may support clot dissolution, oxidised Lp(a) specifically impairs it, highlighting a distinct atherogenic and thrombotic mechanism tied to Lp(a)'s oxidation state rather than its concentration alone.
Original abstract
Objective: In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis.
Methods: Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples.
Results: Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding-the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis.
Conclusion: This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.