Binding of apoE-rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation.
High density lipoproteins (HDL, d 1.063-1.21 g/ml) are reported to stimulate, to have no effect on, or to inhibit agonist-induced platelet aggregation. We have hypothesized that these conflicting reports might be explained by opposing effects of individual HDL subclasses on platelet aggregability. Physiologic concentrations of HDL3 had little effect on ADP-induced aggregation of washed platelet suspensions, although higher levels were stimulatory. Normal concentrations of HDL2 (0.2-0.4 mg of protein/ml) inhibited aggregation; further fractionation by heparin-Sepharose chromatography identified the particles rich in apolipoprotein E, termed HDL-E, as the major anti-aggregatory subclass. Washed platelets bound radioiodinated HDL-E to a uniform class of saturable sites; they numbered 4,200 per platelet and the KD was 7.9 x 10(-7) M. Binding of HDL-E by platelets, and its anti-aggregatory action, showed a similar rapidity and both occurred within the physiologic concentration range. Moreover, the two processes were independent of the presence of divalent ions and were impaired by chemical modification of the apolipoprotein constituents of HDL-E. We conclude that occupation of cell-surface receptors by HDL-E particles impairs platelet responsiveness to exogenous agonists and that platelet aggregability in the presence of whole HDL may reflect the relative concentrations of the individual subclasses in the particular sample.
Desai
K
K
Department of Medicine, Royal Free Hospital School of Medicine, University of London, Hampstead, United Kingdom.
Bruckdorfer
K R
KR
Hutton
R A
RA
Owen
J S
JS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000954:Antigens, Surface; D001057:Apolipoproteins E / Q000378:metabolism*; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002500:Centrifugation, Isopycnic; D002846:Chromatography, Affinity; D006801:Humans; D008075:Lipoproteins, HDL / Q000145:classification / Q000378:metabolism*; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D010974:Platelet Aggregation
D000954:Antigens, Surface; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D000244:Adenosine Diphosphate