Summary
Although platelets have specific bindingsites for LDL and HDL, it is doubtful whether
lipoproteins modulate platelet functions via receptor-mediated processes. We investigated
platelet-lipoprotein interaction during prolonged incubation with concentrations of
LDL and HDL that saturate the bindingsites within a few minutes. When [3H]arachidonate-labeled human platelets were incubated for 4 h with lipoproteins, part
of the 3H-radioactivity transferred to LDL and to a lesser extent to HDL. The transfer was
temperature-sensitive, unaffected by modification of lysine in LDL or indomethacin
treatment of the platelets, and almost irreversible. [3H]arachidonate transfer to lipoproteins could be mimicked by incubating platelets
with a high concentration of fatty acid free albumin. This showed, that the loss of
3H-radioactivity reflected a decrease in endogenous arachidonate, leading to impaired
aggregation, secretion and thromboxane B2 formation in platelets after stimulation with thrombin but not with arachidonate.
Thus, the decrease in platelet functions seen after long incubation with HDL is caused
by depletion of platelet arachidonate. Despite an even stronger arachidonate depletion
by LDL, this lipoprotein initiated arachidonate metabolism and secretion independent
of specific binding sites for LDL on the platelet. Surprisingly, the major part of
the secretion was preserved when the formation of prostaglandin endoperoxides/ thromboxane
A2 was inhibited with indomethacin. These findings argue against a role for LDL and
HDL receptors in the modulation of platelet functions and are more in favor of lipid
exchange processes between platelets and lipoproteins.
