Platelet-associated and secreted PAF-acetylhydrolase activity in patients with stable angina: sequential changes of the enzyme activity after angioplasty.
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).


METHODS
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.
Goudevenos
J
J
Department of Cardiology, University of Ioannina, Ioannina, Greece.
Tselepis
A D
AD
Vini
M P
MP
Michalis
L
L
Tsoukatos
D C
DC
Elisaf
M
M
Ninio
E
E
Sideris
D A
DA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism* / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000201:enzymology*; D005260:Female; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D006490:Hemostatics; D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D013917:Thrombin