Mechanical endothelial damage results in basic fibroblast growth factor–mediated activation of extracellular signal-regulated kinases
1999
Abstract Background: Endothelial damage, such as that associated with balloon angioplasty or preparation of veins for bypass grafts, results in intimal hyperplasia. Growth factors and cytokines that modulate endothelial cell functions through various intracellular signaling pathways mediate rapid endothelial repair, which may prevent or reduce restenosis. Here we investigated the effect of mechanical injury of endothelial cells on the mitogen-activated kinase signaling pathways, extracellular-signal–regulated kinases (ERKs), C-Jun N-terminal kinase (JNK/SAPK), and p38. Methods: Confluent human umbilical vein endothelial cells or bovine aortic endothelial cells were wounded with a razor blade; mitogen-activated kinase activation was monitored by immunoblotting with antibodies to active ERK, JNK/SAPK, or p38. Results: Wounding of human umbilical vein endothelial cell or bovine aortic endothelial cell monolayers resulted in rapid (5-minute) activation of ERK-1 and –2, which was abolished by monoclonal antibody to basic fibroblast growth factor (FGF-2). This antibody or an inhibitor of ERK activation, PD98059, also blocked endothelial cell migration after the wounding. Thus FGF-2–induced ERK activation mediates the endothelial response to wounding. Conclusions: ERK-1 and -2 are activated by FGF-2 released from endothelial cells in response to injury. Therapeutic strategies aimed at reducing FGF-2–induced intimal hyperplasia should preserve ERK activation in endothelial cells while abolishing it in smooth muscle cells. (Surgery 1999:126:422-7.)
Keywords:
- Mitogen-activated protein kinase
- Vascular endothelial growth factor C
- Cell biology
- Endothelial stem cell
- Human umbilical vein endothelial cell
- Growth factor
- Vascular endothelial growth factor B
- Fibroblast growth factor
- Surgery
- Vascular endothelial growth factor A
- Endocrinology
- Medicine
- Internal medicine
- MAPK/ERK pathway
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