Effects of PPAR-α agonist and IGF-1 on estrogen sulfotransferase in human vascular endothelial and smooth muscle cells

Abstract

Estrogen has a protective role in vascular functions and estrogen levels are modulated by estrogen sulfotransferase(SULT1E1). In this study, we investigated the effects of the peroxisome proliferator-activated receptor-α(PPAR-α) agonist WY14643 and insulin-like growth factor-1(IGF-1) on the expression and activity of SULT1E1 in vascular cells. Human umbilical vein endothelial cells (HUVECs) and human umbilical artery smooth muscle cells (HUASMCs) were primarily cultured from fresh umbilical cord. SULT1E1 was highly expressed in HUVECs and HUASMCs according to immunofluorescence microscopy detection. WY14643 decreased, while IGF-1 increased, SULT1E1 mRNA and SULT1E1 protein levels, as demonstrated by RT-qPCR and western blot analysis, respectively, in the HUVECs and HUASMCs. SULT1E1 activity was indicated by counting the transformed 3H-estradiol sulfate from 3H-labeled 17β-estradiol added into the cell culture medium. The activity of SULT1E1 reduced following treatment with WY14643, whereas SULT1E1 activity was enhanced in the presence of IGF-1. The human SULT1E1 promoter-reporter plasmid was constructed. The activity of the SULT1E1 promoter increased 30-fold compared with the pGL3-basic vector. The PPAR-α agonist WY14643 downregulated, while IGF-1 upregulated, the luciferase activity of the SULT1E1 promoter. In conclusion, the PPAR-α agonist WY14643 and IGF-1 may regulate SULT1E1 expression at the transcriptional level and modulate the levels of active estrogens in endothelial cells and smooth muscle cells, thereby affecting the physiology and pathophysiology of vascular walls.