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Human endothelial cells maintain anti-aggregatory activity for platelets during apoptosis
W Xu1, E J Favaloro, H Medbury
1Department of Oral Pathology and Oral Medicine, University of Sydney, Westmead Hospital Dental Clinical School, Westmead Hospital, NSW, Australia. williamx@dental.wsahs.nsw.gov.au
Thrombosis and Haemostasis
|May 25, 2001
Summary
Apoptotic endothelial cells (EC) maintain anti-platelet aggregation activity, crucial for preventing microthrombi during vascular remodeling and injury. This sustained antithrombotic function relies on nitric oxide and prostacyclin.
Area of Science:
- Endothelial cell biology
- Hemostasis and thrombosis
- Vascular biology
Background:
- Apoptotic endothelial cells (EC) show increased tissue factor and platelet binding.
- However, microthrombi are not typically found with apoptotic endothelium, suggesting maintained anti-aggregatory mechanisms.
- This implies EC retain antithrombotic properties even during apoptosis.
Purpose of the Study:
- To investigate the anti-aggregatory activity of apoptotic endothelium.
- To model apoptotic EC release during microvascular remodeling and traumatic detachment.
- To identify the molecular mechanisms underlying this sustained anti-thrombotic activity.
Main Methods:
- Inducing endothelial cell apoptosis via serum and matrix deprivation.
- Assessing platelet aggregation stimulated by ADP or thrombin using apoptotic and non-apoptotic EC.
- Employing inhibition experiments with L-NAME (nitric oxide synthase inhibitor) and indomethacin (prostacyclin synthesis inhibitor).
- Utilizing latex bead assays to confirm specificity of anti-aggregatory effects.
Main Results:
- Both apoptotic and non-apoptotic endothelium exhibited potent anti-aggregatory activity against ADP- and thrombin-stimulated platelets.
- Inhibition of nitric oxide and prostacyclin pathways significantly reduced the anti-aggregatory effect.
- Latex bead experiments confirmed that the observed inhibition of platelet aggregation was not a non-specific phenomenon.
- Apoptotic EC models demonstrated maintained anti-aggregatory activity.
Conclusions:
- Endothelial cells actively maintain antithrombotic activity during apoptosis.
- This sustained activity is mediated by nitric oxide and prostacyclin.
- These findings are consistent with previously reported maintained urokinase levels and canalicular fragmentation in apoptotic EC.
- Apoptotic EC play a role in preventing thrombosis in physiological and pathological conditions.