Abstract
Involvement of platelet-activating factor (PAF) in atherogenesis has been increasingly recogenized in the past few years. PAF is degraded by the action of a specific enzyme, PAF acetylhydrolase; and the estimation of this enzyme activity in plasma may provide an effective measure for clinical studies of atherosclerotic disorders. Our previous study demonstrated an increased PAF acetylhydrolase activity in plasma from patients with cerebral thrombosis. The higher enzyme activity was accounted for by the increased plasma level of LDL, which had been known to carry a major part of plasma PAF acetylhydrolase. However, it was also true that the higher enzyme activity could not be attributed solely to hyperlipoproteinemia; and we hypothesized that platelet hyperfunction would play a critical role. To test this hypothesis, we have studied the relationship between platelet aggregability and plasma PAF acetylhydrolase activity in patients with ischemic stroke.
Thirty-two consecutive patients with cerebral infarction ranging in age from 49 to 81 (66 ± 9.3) years old and 73 age-matched healthy controls (63 ± 7.3 years old) were studied. Plasma PAF acetylhydrolase activity was determined by the method described by Stafforini and coworkers using [2-acetyl-3H] PAF as the substrate. Platelet aggregation induced either by 40 ng/ml PAF or by 2 μM ADP was observed according to Born.
The incidence of irreversible aggregation in response to 40 ng/ml PAF was significantly higher in patients than in controls (62.5% versus 11.0%, p<0.05). The average maximal aggregation in patients was 53 ± 24.3%, which was significantly higher than that in controls : 30 ± 12.2% (p<0.01). The plasma PAF acetylhydrolase activity in patients and controls were 107 ± 47.9 nmol/ml/min and 78± 34.2 nmol/ml/min, respectively; and there was a statistically significant difference between these two values (p<0.01). Among patients, those whose platelets responded with irreversible aggregation to 40 ng/ml PAF displayed a significantly higher plasma PAF acetylhydrolase activity than those with only reversible aggregation. There was no significant difference in the enzyme activity by the irreversibility of ADP-induced aggregation.
These results suggest that PAF may be involved in platelet hyperfunction in patients with cerebral infarction. Increased plasma PAF acetylhydrolase activity in these patients may be an adaptation to platelet hyperfunction. Augmented platelet function may be associated with increased production of PAF, which may bring about the induction of the metabolizing enzyme, PAF acetylhydrolase.
