Pericytes Regulate Fibrinolytic Function of Brain Capillary Endothelial Cells
Our prior work has shown that astrocytes inhibit fibrinolysis of brain capillary endothelial cells (eg, Stroke 1999:30;1671–1677). The complex cellular microenvironment at the blood-brain barrier includes pericytes, which are adjacent to and share basement membrane with brain capillary endothelial cells. We analyzed the hemostatic regulatory role of pericytes in a blood-brain barrier model consisting of human brain pericytes cultured on transwell membrane inserts with human brain capillary endothelial cells. We measured fibrinolysis proteins and function in media conditioned by 48 hour co-culture of human brain capillary endothelial cells and human brain pericytes, as well as brain capillary endothelial mono-cultures. Compared to endothelial mono-cultures, pericyte-endothelial co-cultures exhibited levels of tissue plasminogen activator (tPA) protein reduced by 50±15% (p<.05). Co-culture preparations showed 32±13% (p<.05) increase in levels of plasminogen activator inhibitor-1 (PAI-1) protein, the primary inhibitor of tPA. tPA activity of co-culture preparations was 54±17% (p<.05) of endothelial mono-culture preparations. These data demonstrate that human brain pericytes have an important hemostatic regulatory role for endothelial-dependent fibrinolysis in vitro. These findings provide further support for brain-specific hemostasis, with pericytes as well as astrocytes playing key regulatory roles.