Background. Several studies demonstrated that Lp(a) play an important role in genesis and development of the atherosclerotic lesions. Nevertheless Lp(a) displays an adjunctive and exclusive thrombotic effect due to a supposed competition of the apo(a) protein moiety with plasminogen for activation and binding either to specific plasminogen receptors at the cell surface or to stabilized fibrin. Moreover, Lp(a), similarly to other lipoproteins, affects the functionality of platelets through its binding to cellular receptors, thus sensitizing platelets to a wide variety of stimulating agents. In the present study the potential role of Lp(a) in the adhesion and aggregation of human platelets was investigated. Methods. Lp(a) was purified from human plasma by lysine-Sepharose affinity chromatography and was used to coat the plastic surface of microplate wells where human platelets were incubated for 1 h in the absence and in the presence of the stimulants 10 mM ADP or 0.1 U/mL thrombin. Results. In this assay system, the adhesion of unstimulated platelets to 50 mug/mL Lp(a) was very low (3.8%), as was the adhesion to BSA (2.9 = %) and to fibrinogen (5.2%), while platelet adhesion was much higher (18.8%) when collagen was used as coating agent. Thrombin markedly increased the adhesion to BSA and to fibrinogen (19.7% and 23.3% respectively), while ADP increased the adhesion to fibrinogen but not to BSA 18.2% and 3.0% respectively). The adhesion of stimulated platelets to Lp(a) was very low (3.0% and 5.6% with ADP and thrombin respectively). Finally, Lp(a) at doses > 30 mug/mL inhibited both the adhesion of thrombin-stimulated platelets to fibrinogen or BSA and the ADP-induced aggregation in a dose-dependent fashion. Conclusion. From our results, we conclude that Lp(a) is not a physiological substrate for adhesion of platelets as we demonstrated that Lp(a) may behave as a potential anti-adhesive and anti-aggregating molecule. Therefore the athero-thrombotic potential of Lp(a) has to be explained by other mechanisms, at the inhibition of plasminogen activation.
Evidence that lipoprotein(a) is not an adhesive and proaggregating molecule for platelets in vitro
LIPPI, Giuseppe;GUIDI, Giancesare;BELLAVITE, Paolo
1998-01-01
Abstract
Background. Several studies demonstrated that Lp(a) play an important role in genesis and development of the atherosclerotic lesions. Nevertheless Lp(a) displays an adjunctive and exclusive thrombotic effect due to a supposed competition of the apo(a) protein moiety with plasminogen for activation and binding either to specific plasminogen receptors at the cell surface or to stabilized fibrin. Moreover, Lp(a), similarly to other lipoproteins, affects the functionality of platelets through its binding to cellular receptors, thus sensitizing platelets to a wide variety of stimulating agents. In the present study the potential role of Lp(a) in the adhesion and aggregation of human platelets was investigated. Methods. Lp(a) was purified from human plasma by lysine-Sepharose affinity chromatography and was used to coat the plastic surface of microplate wells where human platelets were incubated for 1 h in the absence and in the presence of the stimulants 10 mM ADP or 0.1 U/mL thrombin. Results. In this assay system, the adhesion of unstimulated platelets to 50 mug/mL Lp(a) was very low (3.8%), as was the adhesion to BSA (2.9 = %) and to fibrinogen (5.2%), while platelet adhesion was much higher (18.8%) when collagen was used as coating agent. Thrombin markedly increased the adhesion to BSA and to fibrinogen (19.7% and 23.3% respectively), while ADP increased the adhesion to fibrinogen but not to BSA 18.2% and 3.0% respectively). The adhesion of stimulated platelets to Lp(a) was very low (3.0% and 5.6% with ADP and thrombin respectively). Finally, Lp(a) at doses > 30 mug/mL inhibited both the adhesion of thrombin-stimulated platelets to fibrinogen or BSA and the ADP-induced aggregation in a dose-dependent fashion. Conclusion. From our results, we conclude that Lp(a) is not a physiological substrate for adhesion of platelets as we demonstrated that Lp(a) may behave as a potential anti-adhesive and anti-aggregating molecule. Therefore the athero-thrombotic potential of Lp(a) has to be explained by other mechanisms, at the inhibition of plasminogen activation.
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