The aggregation of isolated human platelets in the presence of lipoproteins and prostacyclin.
Addition of prostacyclin (PGI2) temporarily inhibits platelet aggregation and permits the isolation of platelets free from plasma proteins, which have the same sensitivity as those in plasma [Moncada, Radomski & Vargas (1982) Br. J. Pharmacol. 75, 165P]. By using a modification of this technique we have established that platelets isolated from normal subjects aggregate more readily in response to ADP and adrenaline when physiological concentrations of low-density lipoproteins (LDL) are present. At high LDL concentrations spontaneous aggregation occurs. High-density lipoproteins (HDL) and very-low-density lipoproteins (VLDL) had no effect on agonist-induced platelet aggregation at normal concentrations, but HDL sensitized at higher concentrations. These effects by lipoproteins are not accompanied by changes in platelet lipid content. Cyclohexanedione treatment of LDL to modify apolipoproteins appeared to abolish the sensitization effect, indicating that binding to receptors was essential for the effects of LDL. LDL, but not HDL, overcame the inhibitory effect of PGI2 on platelet aggregation, except at very high concentrations of PGI2. PGI2 raised the cyclic AMP content of isolated platelets, but LDL only partially prevented this rise. These results suggest that LDL may have a greater role in platelet aggregation than previously recognized and may also regulate effects of PGI2. These findings may be of relevance to an understanding of cardiovascular diseases.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D002469:Cell Separation; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation / Q000187:drug effects*
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D004837:Epinephrine