Effect of Endothelin-1 on DNA Synthesis and Migration of Cultured Cells
Alexander, Leah Marie
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Many methods have been developed to re-establish normal blood flow in stenosed coronary arteries. One such method used to dilate a stenosed coronary artery is percutaneous transluminal coronary angioplasty (PTCA). However, during this procedure, the endothelial cell and smooth muscle layers are damaged, stimulating vascular smooth muscle cells to migrate toward the lumen of the vessel and proliferate. This migration and proliferation narrows the lumen of the vessel, resulting in a phenomenon known as restenosis. Several growth factors such as platelet-derived growth factor appear to be involved. The recently discovered peptide hormone endothelin-l is also speculated to exhibit similar growth factor activity. Endothelin-l w~s tested for promoting DNA synthesis and cell migration of BALB/c 3T3 fibroblasts, Swiss 3T3 fibroblasts, A-l0 and primary smooth muscle cells, and human umbilical vein endothelial cells. DNA synthesis was determined by conducting assays that indicated 3 H-thymidine incorporation into cellular DNA; chemotaxis assays using Boyden blind-well chemotaxis chambers were performed to test cell migration. Results from these tests were compared to the efficacy of platelet-derived growth factor for the fibroblasts and smooth muscle cells and of bovine pituitary extract for the endothelial cells. It was found that endothelin-1 is an effective agent for cell migration in endothelial cells. However, endothelin-1 is only marginally effective in promoting DNA synthesis and cell migration in fibroblasts and smooth muscle cells. These results suggest that endothelin-1 has a relatively minor role in the events that lead to restenosis following PTCA.