Platelet reactivity and arachidonic acid metabolism in type II hyperlipoproteinaemia and its modification by cholesterol-lowering agents.
A significant percentage of patients suffering from a selective increase in plasma LDL cholesterol (type IIa hyperlipoproteinaemia) exhibits increased platelet reactivity. This includes enhanced platelet responsiveness against a variety of platelet-stimulating agents ex vivo and enhanced arachidonic acid metabolism associated with increased generation of arachidonic acid metabolites (thromboxane A2, 12-HETE) and secretion of platelet-storage products. It is possible, but not proven, that an elevated cholesterol content in the platelet membranes forms a common denominator for these responses. Agents that lower total plasma or LDL cholesterol in hypercholesterolaemic patients by interfering with cholesterol reabsorption from the gut (cholestyramine, cholestipol) or reduction of hepatic VLDL release (fibrates) do not appear to interfere with platelet hyperreactivity and do not change platelet-derived thromboxane formation. There is also no correlation with the action of these agents on total plasma and LDL cholesterol. A different situation might exist with inhibitors of the HMG-CoA reductase, which have been found to reduce platelet hyperreactivity and thromboxane formation. However, this finding requires further confirmation in controlled, prospective, large trials. There is increasing evidence that patients with type II hyperlipoproteinaemia have a significant (by about 50%) reduced number of specific prostacyclin binding sites at the platelet membrane that might be involved in the reduced inhibition of platelet function by prostacyclin. Normalization of the reduced responsiveness against prostacyclin has also been demonstrated for cholestyramine and simvastatin. However, so far this issue has not been addressed for the other lipid-lowering compounds.
Schrör
K
K
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood* / Q000188:drug therapy; D008074:Lipoproteins / Q000097:blood; D015230:Prostaglandin D2 / Q000494:pharmacology; D013931:Thromboxanes / Q000097:blood
D000924:Anticholesteremic Agents; D001095:Arachidonic Acids; D008074:Lipoproteins; D013931:Thromboxanes; D016718:Arachidonic Acid; D002784:Cholesterol; D011464:Epoprostenol; D015230:Prostaglandin D2