Lipoprotein(a): Cellular Effects and Molecular Mechanisms
Figure 1
Prothrombotic actions of Lp(a). (a) Plasminogen is activated in a ternary complex comprising fibrin and tPA. Mature plasmin encourages thrombolysis and activates TGFβ. TGFβ has both atheroprotective effects (inhibition of SMC migration and proliferation) and atherogenic effects (inhibition of EC migration, induction of EC cell surface adhesion molecules). (b) Under conditions of elevated plasma Lp(a), plasminogen activation is impaired by multiple mechanisms: Lp(a) competes with plasminogen and tPA for fibrin binding (1). In addition, Lp(a) increases expression of PAI-1 (2) and associates with SERPIN1A (3), both leading to inhibition of tPA. Finally, Lp(a) can associate with α2-macroglobulin, a plasmin inhibitor (4). In combination, all these factors promote a prothrombotic environment.
