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Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells

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Abstract

Purpose

To investigate the toxic effect of oscillating high glucose (OHG) versus persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis in human coronary artery endothelial cells (HCAECs) in vitro.

Methods

HCAECs were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h) and mannitol, respectively. Cellular viability, concentration of oxidative stress biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular ROS level were quantitated after exposure to different concentrations of glucose for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was evaluated by annexin V-FITC and PI staining followed by analysis with flow cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western blotting at the end of the experiment.

Results

HCAECs cultured with PHG showed decreased cellular viability compared to those with normal level of glucose (p < 0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA level, reduced GSH concentration and elevated ROS production (p < 0.05). The stress was further amplified in the setting of OHG (p < 0.05). The cellular apoptosis was enhanced by culturing with PHG, and to a greater extent when incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs in persistent hyperglycemia condition, while the inhibition was more intense in the fluctuating hyperglycemia condition (p < 0.05).

Conclusions

These findings indicate that OHG could be more detrimental to HCAECs than PHG. This is probably due to the enhancement of oxidative stress and cellular apoptosis induced by frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.

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Conflict of interest

None of the authors had a financial interest or professional or personal affiliation that compromises the scientific integrity of this work.

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Authors and Affiliations

  1. Department of Cardiology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, 210002, People’s Republic of China

    Ting-song Liu, Ying-hao Pei, Yong-ping Peng, Shi-sen Jiang & Jian-bin Gong

  2. Department of Emergency Medicine, Nanjing University, School of Medicine, Nanjing, 210002, People’s Republic of China

    Jiao Chen

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  1. Ting-song Liu
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  2. Ying-hao Pei
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  3. Yong-ping Peng
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  4. Jiao Chen
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Correspondence to Jian-bin Gong.

Additional information

T. Liu and Y. Pei contributed equally to this work.

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Liu, Ts., Pei, Yh., Peng, Yp. et al. Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells. J Endocrinol Invest 37, 645–651 (2014). https://doi.org/10.1007/s40618-014-0086-5

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  • DOI: https://doi.org/10.1007/s40618-014-0086-5

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