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Brain endothelial hemostasis regulation by pericytes
Jeong Ai Kim1, Nam D Tran, Zhen Li
1Department of Neurology, University of California, Irvine, California, USA.
Summary
Human brain pericytes regulate hemostasis by decreasing fibrinolysis and potentially providing anticoagulant activity through protease nexin-1 (PN-1). This research defines their hemostatic role in the brain.
Area of Science:
- Neuroscience
- Hematology
- Cell Biology
Background:
- Pericytes are crucial for brain capillary endothelial cell function.
- Their specific role in regulating brain hemostasis remains incompletely defined.
Purpose of the Study:
- To elucidate the hemostatic regulatory function of human brain pericytes.
- To investigate pericyte interactions with endothelial cells in models of the blood-brain barrier.
Main Methods:
- Utilized in vitro blood-brain barrier models with human pericytes and human brain microvascular endothelial cells (HBEC).
- Assessed changes in tissue plasminogen activator (tPA) mRNA and protein levels under co-culture conditions.
- Investigated the impact of lipopolysaccharide (LPS) on inflammatory responses and PAI-1 release.
- Quantified the expression of protease nexin-1 (PN-1) by pericytes.
Main Results:
- Pericyte co-culture significantly decreased endothelial tPA mRNA and protein levels, indicating reduced fibrinolysis.
- Direct contact between pericytes and endothelial cells further enhanced the reduction in tPA.
- Endotoxin (LPS) amplified pericyte-induced plasminogen activator inhibitor-1 (PAI-1) release.
- Pericytes were identified as the primary source of PN-1, an inhibitor with antithrombin effects.
Conclusions:
- Human brain pericytes negatively regulate fibrinolysis in brain endothelial cells.
- Pericyte-derived PN-1 may contribute to endogenous anticoagulant activity within the brain.
- These findings highlight the significant hemostatic role of pericytes in the neurovascular unit.