Indoxyl Sulfate Promotes Proliferation of Human Aortic Smooth Muscle Cells by Inducing Oxidative Stress

Objectives: Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. We have recently demonstrated that indoxyl sulfate (IS), a uremic toxin, induced aortic calcification and aortic wall thickening in hypertensive rats. This study aimed to determine if IS promotes proliferation of human aortic smooth muscle cells (HASMCs) and if antioxidants inhibit the IS-induced cell proliferation. Methods: We examined the effect of IS at different concentration from 50 to 500 mu mol/L on cell proliferation of HASMCs by using 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. Further, the effect of antioxidants such as vitamin E, vitamin C, and N-acetylcysteine on the IS-induced proliferation of HASMCs was determined. Results: IS significantly promoted the proliferation of HASMCs concentration-dependently. The antioxidants significantly inhibited the IS-induced proliferation of HASMCs. Conclusion: IS promotes proliferation of HASMCs by inducing oxidative stress. (C) 2009 by the National Kidney Foundation, Inc. All rights reserved.