Hydrogen peroxide prevents vascular calcification induced ROS production by regulating Nrf-2 pathway.
BACKGROUND
Although vascular calcification in end-stage renal disease (ESRD) represents a ubiquitous human health problem, effective therapies with limited side effects are still lacking, and the precise mechanisms are not fully understood. The Nrf-2/ARE pathway is a pivotal to regulate anti-oxidative responses in vascular calcification upon ESRD. Although Nrf-2 plays a crucial role in atherosclerosis, pulmonary fibrosis, and brain ischemia, the effect of Nrf-2 and oxidative stress on vascular calcification in ESRD patients is still unclear. The aim of this research was to study the protective role of hydrogen peroxide in vascular calcification and the mechanism of Nrf-2 and oxidative stress on vascular calcification.


METHODS
Here we used the rat vascular smooth muscle cell model of β-glycerophosphate-induced calcification resembling vascular calcification in ESRD to investigate the therapeutic effect of 0.01 mM hydrogen peroxide on vascular calcification and further explores the possible underlying mechanisms.


RESULTS
Our current report shows the in vitro role of 0.01 mM hydrogen peroxide in protecting against intracellular ROS accumulation upon vascular calcification. Both hydrogen peroxide and sulforaphane pretreatment reduced ROS production, increased the expression of Nrf-2, and decreased the expression of Runx2 following calcification.


CONCLUSIONS
Our study demonstrates that 0.01 mM hydrogen peroxide can effectively protect rat aortic vascular smooth muscle cells against oxidative stress by preventing vascular calcification induced ROS production through Nrf-2 pathway. These data might define an antioxidant role of hydrogen peroxide in vascular calcification upon ESRD.
a Department of Nephrology , University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital , Chengdu , China.
Wensong
W
Zhang
a Department of Nephrology , University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital , Chengdu , China.
Yi
Y
Li
a Department of Nephrology , University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital , Chengdu , China.
Hanlu
H
Ding
a Department of Nephrology , University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital , Chengdu , China.
Yaqin
Y
Du
a Department of Nephrology , University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital , Chengdu , China.
Li
L
Wang
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D005994:Glycerophosphates / Q000633:toxicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications*; D032389:Myocytes, Smooth Muscle; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D061205:Vascular Calcification / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D000975:Antioxidants; D005994:Glycerophosphates; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C031463:beta-glycerophosphoric acid
ESRD; Nrf-2; hydrogen peroxide; oxidative stress; vascular calcification