Figure 7. Complex effects of apo(a) on endothelial cell function.

(1) Through a mechanism involving, in a manner yet to be defined, integrin α_Vβ₃, apo(a) induces Src and MAP kinase activation that results in increased migration and proliferation [29]. (2) Through binding to a cell surface receptor that is currently undefined, apo(a) results in activation of Rho, which through its effector Rho kinase (RhoK) ultimately results in actin/myosin stress fiber formation and increased endothelial cell contraction and vascular permeability [9]. In addition, through the dissociation of β-catenin form adherens junction and the promotion of β-catenin nuclear translocation through activation of Akt, apo(a) elicits an increase in the expression of cyclooxygenase-2 which results in increased synthesis of prostaglandin E2 (PGE₂) (unpublished observations). (3) Apo(a) inhibits pericellular plasminogen activation that is likely dependent on uPA and the uPA receptor (uPAR), an effect that results in a decrease in tube formation (current study). (4) Through unknown mechanisms, apo(a) results in increases in the expression of several adhesion molecule genes including ICAM-1 and E-selectin [4].