Indoxyl sulfate promotes proliferation of human aortic smooth muscle cells by inducing oxidative stress.
OBJECTIVE
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 mumol/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.


CONCLUSIONS
IS promotes proliferation of HASMCs by inducing oxidative stress.
Muteliefu
Gulinuer
G
Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.
Enomoto
Atsushi
A
Niwa
Toshimitsu
T
D000975:Antioxidants / Q000494:pharmacology*; D001024:Aortic Valve Stenosis / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007200:Indican / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*
D000975:Antioxidants; D007200:Indican