Background: Platelet-activating factor (PAF), the lipid mediator of inflammation and potent platelet agonist, can be hydrolysed and inactivated by PAF-acetylhydrolase (PAF-AH). We investigated the PAF-AH activity in relation to PAF formation in platelets from patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty (PTCA).
Design: Twenty-seven patients with stable angina, undergoing PTCA, and 30 age- and sex-matched controls were studied. The platelet-associated and secreted PAF-AH activity was measured, before PTCA, as well as at 4 h, 48 h and 6 months afterwards. PAF formation by thrombin-stimulated platelets and the platelet aggregation responses to PAF and ADP were also determined.
Results: The PAF-AH activity secreted by thrombin-stimulated platelets before PTCA (in pmol/10(9) cells/h) was significantly higher compared to controls (892 +/- 222 vs. 624 +/- 144, P < 0.001). The enzyme activity was not altered at 4 h after PTCA, but was significantly increased at 48 h (1284 +/- 312, P < 0.005) to return to the levels observed in the control group 6 months afterwards. Detectable levels of PAF in thrombin-stimulated platelets were found only at 6 months after PTCA. Furthermore, the cell-associated enzyme activity in resting platelets before PTCA was significantly lower compared with controls. Unlike in controls, the platelet-associated enzyme activity in the patient group was not increased after stimulation with thrombin and it was associated by a platelet hyperaggregability to PAF. Both the intact cell-associated activity and the platelet hyper-reactivity to PAF were restored at 6 months after PTCA.
Conclusions: Alterations in the platelet PAF-AH activity, which affect the PAF formation in thrombin-stimulated platelets and are associated by an increased aggregatory response to PAF, are observed in patients with stable angina and are completely restored after PTCA.