Apolipoprotein (a) mediates the lipoprotein (a)-induced biphasic shift in human platelet cyclic AMP.
Lipoproteins are known to influence platelet cyclic adenosine monophosphate (c-AMP) levels. Lipoprotein (a) (Lp(a))'s impact on platelet c-AMP levels has never been assessed. Increasing levels of purified human Lp(a) (1-100) mg/dl were incubated with washed human platelets. Lp(a) concentrations of 1-25 mg/dl resulted an initial statistically significant increase of platelet c-AMP above basal levels and decreased collagen-stimulated platelet aggregation levels. Higher concentrations progressively returned the platelet c-AMP concentrations to basal levels accompanied by further decreases in platelet aggregation. Increasing concentrations of purified apolipoprotein (a) (apo(a)) also resulted in a similar biphasic c-AMP response while Lp(a) without apo(a) was without impact. One antibody directed against apo(a) in intact Lp(a) removed the biphasic c-AMP pattern and eliminated Lp(a) platelet aggregation. Antibodies directed against apo B in intact Lp(a) gave results similar to intact Lp(a) in terms of the biphasic response of c-AMP upon platelet exposure to increasing levels of Lp(a). It is concluded that apo(a) mediates the Lp(a)-induced biphasic response in platelet c-AMP as the result of platelet exposure to increasing levels of Lp(a). The biphasic response in c-AMP assists in platelet aggregation decreases up to a concentration of 25 mg/dl Lp(a), such assistance being lost at higher Lp(a) concentrations.
Barre
D E
DE
University College of Cape Breton, P.O. Box 5300, Sydney, Nova Scotia, Canada B1P-6L2. edbarre@ns.sympatico.ca
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001054:Apolipoproteins A / Q000276:immunology / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry*; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D001054:Apolipoproteins A; D017270:Lipoprotein(a); D003094:Collagen; D000242:Cyclic AMP