Lipoprotein(a) inhibits collagen-induced aggregation of thrombocytes.
Lipoprotein(a) [Lp(a)] is known to interact with human platelets in vitro. In the present study the effect of physiological concentrations of Lp(a) on platelet aggregation was studied. Freshly prepared gel-filtered platelets from healthy donors were incubated for 30 minutes at 37 degrees C with various concentrations of Lp(a); aggregation was triggered with ADP, thrombin, and collagen. Control incubations were performed with Tyrode's solution or LDL. Thrombin- and ADP-triggered aggregations were only slightly influenced by Lp(a), but aggregation of platelets stimulated with collagen (4 micrograms/mL) was markedly inhibited. Measurable effects occurred at low concentrations (0.05 mg/mL) of total Lp(a); at 0.5 mg/mL, maximum aggregation of platelets was inhibited by 54 +/- 20%, and the aggregation rate was attenuated by 47 +/- 19% compared with platelets incubated with Tyrode's solution. Preincubation of collagen (4 micrograms/mL) with Lp(a) yielded similar results. The effect of Lp(a) on platelet aggregation was accompanied by a significant reduction of serotonin release and TXA2 formation. Higher concentrations of collagen ( > or = 10 micrograms/ mL) caused the inhibitory effect on Lp(a) on collagen-induced aggregation to disappear. In contrast, incubation of platelets with 5 mg/mL LDL led to a significant increase of aggregation rate, maximum aggregation, serotonin release, and formation of TXA2 when aggregation was induced with 4 micrograms/mL collagen. In an adhesion assay using fresh whole blood, which mimics the in vitro situation of vessel injury. Lp(a) reduced platelet adhesion at shear rates of 300 and 1600/s by 22.6% and 11.6%, respectively. In addition, Lp(a) reduced the size of platelet aggregates significantly (up to 63%); this reduction was more distant at the higher shear rate. Unlike LDL, Lp(a) is not a proaggregatory lipoprotein; rather, collagen-triggered aggregation in vitro is attenuated by Lp(a).
Gries
A
A
Institute of Physiology, Graz, Austria.
Gries
M
M
Wurm
H
H
Kenner
T
T
Ijsseldijk
M
M
Sixma
J J
JJ
Kostner
G M
GM
D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D017270:Lipoprotein(a); D012701:Serotonin; D013929:Thromboxane B2; D003094:Collagen