Related Experiment Videos
Thrombin generation by apoptotic vascular smooth muscle cells
P D Flynn1, C D Byrne, T P Baglin
1Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.
Blood
|June 15, 1997
Summary
Apoptotic vascular smooth muscle cells (VSMCs) expose phosphatidylserine, generating significant thrombin. This finding suggests a role for apoptotic cells in local thrombin activation and disease progression, particularly in atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Hemostasis and Thrombosis
- Cellular Biology
Background:
- Thrombin generation is crucial for hemostasis, typically requiring activated platelets.
- Anionic phospholipids, like phosphatidylserine, on cell surfaces are essential for prothrombinase complex assembly.
- Vascular smooth muscle cells (VSMCs) undergoing apoptosis expose phosphatidylserine.
Purpose of the Study:
- To investigate the thrombin-generating capacity of apoptotic VSMCs.
- To compare the procoagulant potential of apoptotic VSMCs with activated platelets.
- To explore the role of apoptotic VSMCs in thrombin generation within atherosclerotic lesions.
Main Methods:
- Chromogenic assay to measure thrombin generation.
- Assessment of thrombin generation in apoptotic rat and human VSMCs (VSMC-myc).
- Inhibition studies using annexin V and comparison with activated platelets.
Main Results:
- Apoptotic VSMC-myc cells demonstrated significant thrombin generation (AUC 305 +/- 17 nmol x min/L, PT 154 +/- 9 nmol/L).
- Thrombin generation by apoptotic VSMCs was comparable to calcium-ionophore activated platelets.
- Apoptotic human VSMCs and VSMCs from atherosclerotic plaques also exhibited thrombin generation.
Conclusions:
- Apoptotic VSMCs possess substantial thrombin-generating capacity due to phosphatidylserine exposure.
- These findings highlight a novel source of local thrombin activation.
- Apoptotic cells in atherosclerotic plaques may contribute to disease progression through thrombin generation.