Publication Date:
2010-11-19
Description:
Abstract 2107 Endothelial cell activation and elevated levels of circulating Endothelin-1 (ET-1) have been reported in patients with atherosclerosis and sickle cell disease (SCD). ET-1 is a well-described vasoconstrictor, mitogen and regulator of endothelial cells migration that has been shown to promote structural changes in blood vessels. ET-1 is produced in response to increases in vasoactive hormones, growth factors, hypoxia, shear stress and free radicals, events that are commonly observed in patients with SCD. Endothelial cell activation is in part characterized by increases of cytokines such as monocyte chemotactic protein-1 (MCP-1) and growth factors that are important in vascular maintenance and fibrogenesis such as connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). CTGF and VEGF are important for blood vessel remodeling, fibrogenesis and angiogenesis. Indeed there is evidence that incubation of smooth muscle cells with ET-1 leads to increases in CTGF and VEGF levels. However, the relationship between ET-1 and CTGF in endothelial cell activation is unclear. We hypothesize that increasing ET-1 would stimulate CTGF production and endothelial cell activation. We studied the effects of ET-1 on the human endothelial cell line, EA.hy926 (EA), as well as in primary cultures of mouse aortic endothelial cells (MAEC). We performed gene expression time course experiments (0, 2, 4, 8, 16, 24 Hr) on EA cells following incubation with 100nM ET-1 using quantitative RT-PCR with Taqman chemistries and GAPDH and beta-actin as endogenous controls. We observed increases of CTGF and VEGF expression between 4 and 8 hr for CTGF (1.74 fold increase vs time 0, n=6, P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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