LEUKOCYTE AND PLATELET-FUNCTION AND EICOSANOID PRODUCTION IN SUBJECTS WITH HYPERCHOLESTEROLEMIA

A group of 22 subjects with type IIA hypercholesterolaemia (mean serum cholesterol = 8.3 ± 0.3 mmol/l) were sex, age and weight matched with 22 control subjects (mean serum cholesterol = 4.5 ± 0.1 mmol/1). Diastolic blood pressure was significantly higher in hypercholesterolaemic subjects (79.2 ± 1.4 mm Hg) than in control subjects (71.9 ± 1.4 mm Hg). While the high cholesterol group had 52% greater thromboxane production in clotted whole blood than controls this difference was not significant, and the platelet aggregation and serotonin secretion response to doses of collagen, ADP and arachidonic acid were similar between the 2 groups. Polymorphonuclear leukocyte (PMN) chemiluminescence (used as a measure of reactive oxygen species production) in response to low doses of the chemotactic peptide FMLP and opsonized zymosan was significantly greater in high cholesterol subjects compared to their matched controls. The production of platelet activating factor (PAF) by calcium ionophore (2.5 μg) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 ± 1.4 ng/106 cells) was significantly greater than PAF production by cells from the control group (8.3 ± 1.0 ng/106 cells). Leukotriene B4 release by PMN in response to calcium ionophore did not differ between the 2 groups. These data suggest a degree of leukocyte activation in hypercholesterolaemic subjects compared to controls with normal cholesterol. In addition, plasma levels of lyso-PAF were higher in high cholesterol subjects (317 ± 21 ng/ml) compared to their matched controls (271 ± 18 ng/ml) perhaps indicating increased plasma acetylhydrolase activity in subjects with raised cholesterol levels. Recently described biological activity for lyso PAF suggests a possible role for this substance in atherogenesis. We could find no difference in cellular phospholipid fatty acid composition between the two groups which would account for the alteration in formation of lipid mediators. The finding of increased reactive oxygen species and PAF formation in stimulated PMN from hypercholesterolaemic subjects together with higher levels of blood lyso-PAF extend our knowledge on the possible influence of raised LDL-cholesterol on the release of lipid mediators which may be involved in atherogenesis. © 1990.