Platelet-activating factor (PAF) stimulates the lysoPAF acetyltransferase in leukocyte-rich plasma: Use in PAF antagonist studies

SummaryPlatelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.

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Phospholipase C from Clostridium Perfringens Induces Human Platelet Aggregation in Plasma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642761 ◽

1988 ◽

Vol 59 (02) ◽

pp. 236-239 ◽

Cited By ~ 2

Author(s):

Giovanna Barzaghi ◽

Chiara Cerletti ◽

Giovanni de Gaetano

Keyword(s):

Platelet Aggregation ◽

Receptor Antagonist ◽

Phospholipase C ◽

Clostridium Perfringens ◽

Human Platelet ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Platelet Activating Factor ◽

Inhibitory Effect ◽

Thromboxane Receptor Antagonist

SummaryWe studied the aggregating effect of different concentrations of phospholipase C (PLC) (extracted from Clostridium perfringens) on human platelet-rich plasma (PRP). PRP was preincubated with PLC for 3 min at 37° C and the platelet aggregation was followed for 10 min. The threshold aggregating concentration (TAG) of PLC was 3-4 U/ml.We also studied the potentiation of PLC with other stimuli on platelet aggregation. Potentiating stimuli, such as arachidonic acid (AA), ADP. Platelet Activating Factor (PAF) and U-46619 (a stable analogue of cyclic endoperoxides) were all used at subthreshold concentrations. We also studied the possible inhibitory effect of aspirin, apyrase, TMQ, a prostaglandin endoper- oxide/thromboxane receptor antagonist and BN-52021, a PAF receptor antagonist. Only aspirin and apyrase were able to reduce aggregation induced by PLC alone and PLC + AA and PLC + ADP respectively. TMQ and BN-52021 were inactive. In ex vivo experiments oral aspirin (500 mg) partially inhibited platelet aggregation induced by PLC alone, PLC + AA and PLC + ADP 2 and 24 h after administration. Aspirin 20 mg for 7 days also reduced aggregation induced by PLC + AA.

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Time Dependence of Whole Blood Aggregation in Response to Platelet Activating Factor (PAF)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642746 ◽

1988 ◽

Vol 59 (02) ◽

pp. 162-163 ◽

Cited By ~ 5

Author(s):

R R Taylor ◽

J Strophair ◽

M Sturm ◽

R Vandongen ◽

L J Beilin

Keyword(s):

Time Dependence ◽

Whole Blood ◽

Platelet Rich Plasma ◽

Platelet Activating Factor ◽

Sampling Time ◽

Blood Sampling ◽

Impedance Aggregometry

SummaryThe aggregation/adhesion response to platelet activating factor (PAF) was studied in diluted whole blood by impedance aggregometry. The extent of aggregation varied directly with the interval between blood sampling and aggregation measurement over the first 30 minutes from sampling, then remained stable for the next 60 minutes of observation. This is an effect opposite to that described for aggregation to PAF in platelet rich plasma which, however, cannot be studied soon after sampling. Time dependence of aggregation is important and comparative measurements should be made during the period of stable aggregability.

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The Role of Platelet-Activating Factor in Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647261 ◽

1990 ◽

Vol 64 (01) ◽

pp. 099-103 ◽

Cited By ~ 39

Author(s):

Stephen M Prescott ◽

Thomas M McIntyre ◽

Guy A Zimmerman

Keyword(s):

Endothelial Cells ◽

Platelet Activating Factor

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Inhibition by Glaucocalyxin A of Aggregation of Rabbit Platelets Induced by ADP, Arachidonic Acid and Platelet-Activating Factor, and Inhibition of [3H]-PAF Binding

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648470 ◽

1992 ◽

Vol 67 (04) ◽

pp. 458-460 ◽

Cited By ~ 12

Author(s):

Zhang Bin ◽

Long Kun

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Activating Factor ◽

Northeastern China ◽

Ethereal Extract ◽

Ic50 Value ◽

Rabbit Platelets ◽

Ic50 Values ◽

Induced Aggregation

SummaryGlaucocalyxin A is a new diterpenoid isolated from the ethereal extract of the leaves of Rabdosia japonica (Burm f) Hara var glaucocalyx (Maxim) Hara (Labiatae) collected in the northeastern China. When it was incubated with washed rabbit platelets, glaucocalyxin A inhibited ADP- or arachidonic acid-induced platelet aggregation with IC50 values of 4.4 μmol/1, 14.1 μmol/1 respectively. Glaucocalyxin A also inhibited PAF-induced aggregation of rabbit platelets which were refractory to ADP and arachidonic acid with an IC50 value of 13.7 μmol/1. Analysis of [3H]-PAF binding showed that glaucocalyxin A prevented [3H]-PAF binding to intact washed rabbit platelets with an IC50 value of 8.16 μmol/1, which was consistent with its inhibition of PAF-induced platelet aggregation.

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Effects of Antithrombotic Drugs in a Rat Model of Aspirin-Insensitive Arterial Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651642 ◽

1993 ◽

Vol 69 (05) ◽

pp. 509-514 ◽

Cited By ~ 28

Author(s):

W A Schumacher ◽

T E Steinbacher ◽

C L Heran ◽

J R Megill ◽

S K Durham

Keyword(s):

Arterial Thrombosis ◽

Light And Electron Microscopy ◽

Platelet Activating Factor ◽

Thrombin Inhibitor ◽

Experimental Conditions ◽

Once Daily ◽

Thromboxane Receptor ◽

Vessel Patency ◽

Electrolytic Injury ◽

Thromboxane Receptor Antagonist

SummaryThese studies describe experimental conditions where aspirin is less effective than other antiplatelet and anticoagulant drugs in inhibiting acute arterial thrombosis. External electrolytic injury of the rat carotid artery was used to induce occlusive thrombi in 97% of vehicle-treated rats. Thrombi were revealed by light and electron microscopy to be comprised primarily of platelets enmeshed in a fibrin network. The thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethy ketone (PPACK; 6 mg/kg, i. v.) decreased thrombus weight by 90%. Aspirin alone (1, 10 and 30 mg/kg, i. v.), dipyridamole alone (5 mg/kg i. v.) and aspirin (1 and 10 mg/kg, i. v.) in combination with dipyridamole (5 mg/kg, i. v.) did not inhibit thrombosis. The platelet-activating factor (PAF) antagonist, WEB 2086, (1 mg/kg i. v.) was also ineffective. Other drugs had intermediate activity. Thrombi were decreased 56% by the thromboxane receptor antagonist, BMS 180,291, either alone (5.8 mg/kg i.v.) or in combination with aspirin (10 mg/kg, i.v.). Heparin (900 U/kg, i.v.), warfarin (0.25 mg/kg, p.o. once daily for 3 days) and ticlopidine (200 mg/ kg, p.o. once daily for 3 days) reduced thrombus weight by 63, 73 and 43% respectively. Reductions in thrombus weight were always associated with improvements in either average blood flow or vessel patency.

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