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Platelet aggregability to platelet activating factor at rest and after exercise in patients with coronary artery
J Goudevenos1, A D Tselepis, D Tsoukatos
1Department of Cardiology, Medical School, University of Ioannina, Greece.
Insights
Platelet-activating factor (PAF) causes increased platelet aggregation in coronary artery disease patients with positive exercise tests. This heightened response, linked to altered PAF-acetylhydrolase (PAF-AH) activity and lipid profiles, suggests a role in cardiovascular disease progression.
Area of Science:
- Cardiovascular Research
- Platelet Physiology
- Lipid Metabolism
Background:
- Platelet-activating factor (PAF) is a potent lipid mediator involved in inflammation and thrombosis.
- Elevated PAF levels and altered PAF-acetylhydrolase (PAF-AH) activity are implicated in cardiovascular diseases.
- The relationship between PAF response, PAF-AH activity, and lipid profiles in coronary artery disease (CAD) patients during exercise stress warrants further investigation.
Purpose of the Study:
- To investigate the platelet response to PAF in CAD patients undergoing exercise tests.
- To correlate platelet aggregation with blood PAF levels, serum PAF-AH activity, and lipidaemic profiles.
- To differentiate these responses between CAD patients with positive and negative exercise test results.
Main Methods:
- Studied 44 CAD patients and 21 normal subjects, assessing platelet-activating factor (PAF) EC50 and maximal aggregation.
- Measured whole-blood PAF levels and serum PAF-acetylhydrolase (PAF-AH) activity at rest and post-exercise.
- Analyzed correlations between PAF response, PAF-AH activity, and serum lipid profiles (total and LDL cholesterol).
Main Results:
- CAD patients with positive exercise tests showed significantly decreased PAF EC50 and increased maximal platelet aggregation at rest compared to controls.
- No significant differences in PAF response were observed in patients with negative exercise tests.
- Elevated resting PAF-AH activity was found in positive exercise test patients, correlating with lipids in controls and negative test groups, but not in positive test patients.
Conclusions:
- CAD patients with positive exercise tests exhibit heightened platelet sensitivity to PAF, independent of exercise-induced changes.
- Increased PAF-AH activity in these patients may be linked to their lipid profiles, but the correlation is lost in the positive exercise test group.
- These findings suggest a potential role for PAF dysregulation and altered PAF-AH activity in the pathophysiology of coronary artery disease.
Abstract:
The platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to blood PAF levels, serum PAF-acetylhydrolase (PAF-AH) activity and to their lipidaemic profile, was studied in 44 patients with coronary artery disease undergoing exercise tests. The PAF EC50 values in 21 patients with positive exercise test results were found to be significantly decreased at rest compared with 21 normal subjects (12.6 +/- 3.9 nM and 24.9 +/- 11.7 nM respectively) (P<0.0001). Moreover, the maximal percentage of aggregation to 50 nM PAF was found to be significantly increased (20.0 +/- 4.3% vs 13.5 +/- 3.6%, respectively) (P<0.0001). By contrast, the PAF EC50 values and the maximal percentage of aggregation in 23 patients with negative exercise test results were not statistically significantly different from the control group (25.2 +/- 11.4 nM and 14.1 +/- 4.7%, respectively). At the end of exercise, the PAF EC50 values and the maximal percentage of aggregation did not change in any group, and there were no significant differences in the whole-blood PAF levels either at rest or at the end of exercise. In patients with positive exercise test results, the PAF-AH activity at rest was significantly higher compared with the control group (37.2 +/- 8.0 nmol.ml(-1).min(-1) vs 32.4 nmol.ml(-1).min(-1), (P<0.03), whereas the enzyme activity did not differ in patients with negative exercise test results compared to controls (33.6 +/- 6.1 nmol.ml(-1).min(-1)). There was no change in PAF-AH activity during exercise in any group. The enzyme activity was positively correlated to the serum total and low density lipoprotein (LDL) cholesterol levels in the control group and in patients with negative exercise test results, whereas no correlation was found between PAF-AH activity and total or LDL cholesterol levels in patients with positive exercise test results.