Estradiol down-regulates MCP-1 expression in human coronary artery endothelial cells

Abstract

Objective: To determine whether estrogen down-regulates MCP-1 in vascular endothelial cells. Design: A prospective comparative study. Setting: Academic research environment. Patient(s): Human umbilical vein endothelial cells (n = 3) and human coronary artery endothelial cells (n = 3) obtained from females. Intervention(s): Human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) were grown to preconfluence. Then, they were treated with various concentrations of estradiol (10 −11 M to 10 −7 M) as well as raloxifene (10 −7 M) and tamoxifen (10 −7 M). MCP-1 in culture media was quantified using an enzyme-linked immunosorbent assay (ELISA). Cellular ribonucleic acid (RNA) was extracted and Northern blots were hybridized with an oligonucleotide probe complementary to a specific sequence of MCP-1 mRNA. Main Outcome Measure(s): MCP-1 protein and mRNA. Result(s): Estrogen treatment did not change MCP-1 expression in HUVEC. On the other hand, in HCAEC, estradiol induced a 30% decrease in mRNA expression and resulted in dose-dependent inhibition of MCP-1 production as detected by ELISA. Raloxifene and tamoxifen also resulted in inhibition of MCP-1 mRNA and protein expression. Conclusion(s): Our findings suggest that one of the mechanisms by which estrogen down-regulates atherosclerosis is by suppressing vascular MCP-1 expression, resulting in decreased macrophage recruitment.