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Pathologic high shear stress induces apoptosis events in human platelets
Valery Leytin1, David J Allen, Sergiy Mykhaylov
1Division of Transfusion Medicine, Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ont., Canada M5B 1W8. leytinv@smh.toronto.on.ca
Biochemical and Biophysical Research Communications
|June 29, 2004
Summary
Pathologic shear stresses, not physiologic levels, induce apoptosis in anucleate platelets. This finding reveals a novel mechanism for platelet programmed cell death mediated by mechanical forces.
Area of Science:
- Biomedical Engineering
- Hematology
- Cell Biology
Background:
- Platelet apoptosis can be induced by chemical agonists.
- Mechanical forces (shear stresses) are known to stimulate platelet activation and signaling.
- The effect of shear stress on platelet apoptosis has not been previously studied.
Purpose of the Study:
- To investigate whether shear stresses can trigger apoptosis in anucleate platelets.
- To determine the threshold of shear stress required to induce platelet apoptosis.
- To elucidate the mechanisms underlying shear-induced platelet apoptosis.
Main Methods:
- Human platelet-rich plasma was exposed to varying shear stresses using a cone-and-plate viscometer.
- Shear stress levels ranged from physiologic (10-44 dyn/cm²) to pathologic (117-388 dyn/cm²).
- Platelet activation markers (P-selectin, GPIbalpha) and apoptosis events were analyzed.
Main Results:
- Pathologic shear stresses induced platelet activation, including P-selectin upregulation and GPIbalpha downregulation.
- Pathologic shear stresses triggered key apoptosis events: mitochondrial depolarization, caspase 3 activation, phosphatidylserine exposure, and platelet shrinkage/fragmentation.
- Physiologic shear stresses did not induce platelet activation or apoptosis.
Conclusions:
- Pathologic shear stresses can induce anucleate platelet apoptosis.
- Shear-induced platelet apoptosis is likely mediated by mechanoreceptors and does not require nuclear participation.
- This finding may have implications for understanding platelet clearance in conditions with abnormal blood flow.