Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia.
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/l). 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 micrograms) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 +/- 1.4 ng/10(6) cells) was significantly greater than PAF production by cells from the control group (8.3 +/- 1.0 ng/10(6) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Croft
K D
KD
Department of Medicine, University of Western Australia, Perth.
Beilin
L J
LJ
Vandongen
R
R
Rouse
I
I
Masarei
J
J
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D007975:Leukotriene B4 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D001095:Arachidonic Acids; D005227:Fatty Acids; D008055:Lipids; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D016718:Arachidonic Acid; D012701:Serotonin; D000001:Calcimycin; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen