Abstract
Altered blood shear stress is one of the risk factors that can induce platelet activation, thrombosis, atherosclerosis and many other cardiovascular diseases. Complement activation, an important contributor in inflammation, has also been reported to be related to blood flow induced platelet activation. In this study, the dose effect of shear stress (magnitude and shear exposure time) on platelet surface complement activation was investigated, using a dynamic cone and plate shearing device. Washed platelets were exposed to uniformly distributed shear stresses at 2.4 or 9 dyne/cm2 for 30 min. Timed samples at 0, 10, 20 and 30 min were taken and assayed for complement activation (C4d, C3b and C5b‐9 deposition) using a solid phase ELISA approach. In parallel, platelet activation was examined using flow cytometry for CD62P expression, and a modified prothrombinase assay for thrombin generation. Results indicate that activated platelets support complement activation to completion, with the production of membrane attack complex (C5b‐9). The generation of complement activation products, C4d, C3b and C5b‐9, increased significantly as shear stress magnitude and shear exposure time increased, correlating to platelet activation levels. Therefore, platelet activation and its associated complement activation may interact and promote cardiovascular disease development under pathological shear conditions.
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