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Fibrinogen induces chemotactic activity in endothelial cells
1Innere Medizin III, Universität Heidelberg, Heidelberg, Germany.
Acta Physiologica Scandinavica
|October 2, 2002
Summary
Fibrinogen, an extracellular matrix protein, significantly increases the secretion of monocyte chemoattractants by endothelial cells. This process involves integrin signaling and protein kinase C, contributing to early atherogenesis.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Biochemistry
Background:
- Atherogenesis involves monocyte recruitment and extracellular matrix (ECM) changes.
- Endothelial cells (EC) play a crucial role in regulating monocyte chemotaxis.
Purpose of the Study:
- To investigate how ECM proteins influence chemoattractant secretion by endothelial cells.
- To elucidate the signaling pathways involved in ECM-mediated monocyte chemotaxis.
Main Methods:
- Porcine EC were cultured on different ECM proteins (gelatin, fibronectin, fibrinogen).
- Monocyte chemotactic activity in EC supernatants was measured.
- Secretion of specific chemokines (MCP-1, PDGF-AB, IL-8) was quantified.
- Integrin binding and protein kinase C (PKC) signaling pathways were inhibited.
Main Results:
- Fibrinogen (Fg) significantly increased monocyte chemotactic activity and chemokine secretion compared to gelatin (G).
- Fg-induced chemotaxis was dependent on integrin binding and mediated by protein kinase C (PKC) signaling.
- Fg induced the PKC isoform delta, indicating pathway activation.
Conclusions:
- Fibrinogen binding to integrins initiates an intracellular signaling cascade (PKC pathway).
- This pathway leads to increased secretion of chemokines, promoting monocyte recruitment.
- ECM protein-mediated signaling, particularly by fibrinogen, is a key mechanism in early atherogenesis.