Skip to main content
SpringerLink
Log in

ROS and NO Dynamics in Endothelial Cells Exposed to Exercise-Induced Wall Shear Stress

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

Introduction

Intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels are associated with vascular homeostasis and diseases. Exercise can modulate ROS and NO production through increasing frequency and magnitude of wall shear stress (WSS). However, the details of ROS and NO production in endothelial cells and their interplay under WSS induced by exercise at different intensities remain unclear.

Methods

In this study, we developed an in vitro multicomponent nonrectangular flow chamber system to simulate pulsatile WSS waveforms induced by moderate and high intensity exercise. Furthermore, the dynamic responses of ROS and NO in endothelial cells and the relationship between ROS and NO were investigated under the WSS induced by different intensity exercise.

Results

After exposing to WSS induced by moderate intensity exercise, endothelial cells produced more NO than those under high intensity exercise-induced WSS. In this process, ROS was found to play a dual role in the generation of intracellular NO. Under WSS induced by moderate intensity exercise, modest elevated ROS promoted NO production, whereas excessive ROS in endothelial cells exposed to WSS induced by high intensity exercise attenuated NO bioavailability. Interestingly, antioxidant N-acetylcysteine (NAC) could increase NO production under WSS induced by high intensity exercise.

Conclusions

Our results provide some cues for selecting appropriate exercise intensities and elevating benefits of exercise on endothelial function. Additionally, owing to the consistency of our results and some in vivo phenomena, this flow chamber system may serve as an in vitro exercise model of arterial vessel for future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Aruoma, O. I. Characterization of drugs as antioxidant prophylactics. Free Radic. Biol. Med. 20(5):675–705, 1996.

    Article  Google Scholar 

  2. Battault, S., F. Singh, S. Gayrard, J. Zoll, C. Reboul, and G. Meyer. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling. Hypertens. Res. 39(2):70, 2016.

    Article  Google Scholar 

  3. Beck, D. T., J. S. Martin, D. P. Casey, and R. W. Braith. Exercise training improves endothelial function in resistance arteries of young prehypertensives. J. Hum. Hypertens. 28(5):303, 2014.

    Article  Google Scholar 

  4. Bharath, L. P., R. Mueller, Y. Li, T. Ruan, D. Kunz, R. Goodrich, T. Mills, L. Deeter, A. Sargsyan, P. V. A. Babu, T. E. Graham, and J. D. Symons. Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability. Can. J. Physiol. Pharmacol. 92(7):605–612, 2014.

    Article  Google Scholar 

  5. Birk, G. K., E. A. Dawson, C. Atkinson, A. Haynes, N. T. Cable, D. H. Thijssen, and D. J. Green. Brachial artery adaptation to lower limb exercise training: role of shear stress. J. Appl. Physiol. 112(10):1653–1658, 2012.

    Article  Google Scholar 

  6. Blackman, B. R., G. Garcıa-Cardena, and M. A. Gimbrone. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J. Biomech. Eng. 124(4):397–407, 2002.

    Article  Google Scholar 

  7. Chao, Y., P. Ye, L. Zhu, X. Kong, X. Qu, J. Zhang, J. Luo, H. Yang, and S. Chen. Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway. J. Cell. Physiol. 233(2):1384–1395, 2018.

    Article  Google Scholar 

  8. Chien, S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am. J. Physiol Heart Circ. Physiol. 292(3):H1209–H1224, 2007.

    Article  Google Scholar 

  9. Chin, L. K., J. Q. Yu, Y. Fu, T. Yu, A. Q. Liu, and K. Q. Luo. Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations. Lab Chip. 11(11):1856–1863, 2011.

    Article  Google Scholar 

  10. Foncea, R., C. Carvajal, C. Almarza, and F. Leighton. Endothelial cell oxidative stress and signal transduction. Biol. Res. 33(2):89, 2000.

    Article  Google Scholar 

  11. Förstermann, U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch. 459(6):923–939, 2010.

    Article  Google Scholar 

  12. Goto, C., Y. Higashi, M. Kimura, K. Noma, K. Hara, K. Nakagawa, M. Kawamura, K. Chayama, M. Yoshizumi, and I. Nara. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation. 108(5):530–535, 2003.

    Article  Google Scholar 

  13. Gray, K. M., and K. M. Stroka. Vascular endothelial cell mechanosensing: new insights gained from biomimetic microfluidic models. Semin. Cell Dev. Biol. 71:106–117, 2017.

    Article  Google Scholar 

  14. Green, D. J., T. Eijsvogels, Y. M. Bouts, A. J. Maiorana, L. H. Naylor, R. R. Scholten, M. E. A. Spaanderman, C. J. A. Pugh, V. S. Sprung, T. Schreuder, H. Jones, T. Cable, M. T. E. Hopman, and D. H. J. Thijssen. Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors. J. Appl. Physiol. 117(4):345–352, 2014.

    Article  Google Scholar 

  15. Hambrecht, R., V. Adams, S. Erbs, A. Linke, N. Kränkel, Y. Shu, Y. Baither, S. Gielen, H. Thiele, J. F. Gummert, F. W. Mohr, and G. Schuler. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 107(25):3152–3158, 2003.

    Article  Google Scholar 

  16. Han, Y., L. Wang, Q. P. Yao, P. Zhang, B. Liu, G. L. Wang, B. R. Shen, B. C. Chen, Y. X. Wang, Z. L. Jiang, and Y. X. Qi. Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress. Biochim. Biophys. Acta 1853(5):1165–1173, 2015.

    Article  Google Scholar 

  17. Higashi, Y., and M. Yoshizumi. New methods to evaluate endothelial function: method for assessing endothelial function in humans using a strain-gauge plethysmography: nitric oxide-dependent and-independent vasodilation. J. Pharmacol. Sci. 93(4):399–404, 2003.

    Article  Google Scholar 

  18. Hsiai, T. K., J. Hwang, M. L. Barr, A. Correa, R. Hamilton, M. Alavi, M. Rouhanizadeh, and S. L. Hazen. Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration. Free Radic Biol. Med. 42(4):519–529, 2007.

    Article  Google Scholar 

  19. Hsieh, H. J., C. C. Cheng, S. T. Wu, J. J. Chiu, B. S. Wung, and D. L. Wang. Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression. J. Cell. Physiol. 175(2):156–162, 1998.

    Article  Google Scholar 

  20. Hsieh, H. J., C. A. Liu, B. Huang, A. H. Tseng, and D. L. Wang. Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J. Biomed. Sci. 21(1):3, 2014.

    Article  Google Scholar 

  21. Johnson, B. D., J. Padilla, and J. P. Wallace. The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men. Eur. J. Appl. Physiol. 112(1):33–42, 2012.

    Article  Google Scholar 

  22. Kang, H., Y. Fan, and X. Deng. Vascular smooth muscle cell glycocalyx modulates shear-induced proliferation, migration, and NO production responses. Am. J. Physiol. Heart Circ. Physiol. 300(1):H76–H83, 2010.

    Article  Google Scholar 

  23. Kim, B., H. Lee, K. Kawata, and J. Y. Park. Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium. PLoS ONE 9(11):e111409, 2014.

    Article  Google Scholar 

  24. Laughlin, M. H., and R. M. McAllister. Exercise training-induced coronary vascular adaptation. J. Appl. Physiol. 73(6):2209–2225, 1992.

    Article  Google Scholar 

  25. Liu, H. B., W. X. Yuan, K. R. Qin, and J. Hou. Acute effect of cycling intervention on carotid arterial hemodynamics: basketball athletes versus sedentary controls. Biomed. Eng. Online. 14(1):S17, 2015.

    Article  Google Scholar 

  26. Lum, H., and K. A. Roebuck. Oxidant stress and endothelial cell dysfunction. Am. J. Physiol Cell Physiol. 280(4):C719–C741, 2001.

    Article  Google Scholar 

  27. Pan, S. Molecular mechanisms responsible for the atheroprotective effects of laminar shear stress. Antioxid. Redox Signal. 11(7):1669–1682, 2009.

    Article  Google Scholar 

  28. Schirmer, S. H., A. Degen, M. Baumhäkel, F. Custodis, L. Schuh, M. Kohlhaas, E. Friedrich, F. Bahlmann, R. Kappl, C. Maack, and M. Böhm. Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis. Eur. Heart J. 33(10):1223–1231, 2011.

    Article  Google Scholar 

  29. Shafique, E., A. Torina, Y. Liu, J. Feng, L. Benjamin, E. Harrington, F. Sellke, and R. Abid. Oxidant-induced endothelial dysfunction is a failure of the mitochondria to process cytosolic ROS. Eur. J. Pharmacol. 480(1–3):43–50, 2003.

    Google Scholar 

  30. Silvestro, A., F. Scopacasa, G. Oliva, C. T. De, L. Iuliano, and G. Brevetti. Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication. Atherosclerosis. 165(2):277–283, 2002.

    Article  Google Scholar 

  31. Sun, M. W., M. F. Zhong, J. Gu, F. L. Qian, J. Z. Gu, and H. Chen. Effects of different levels of exercise volume on endothelium-dependent vasodilation: roles of nitric oxide synthase and heme oxygenase. Hypertens. Res. 31(4):805, 2008.

    Article  Google Scholar 

  32. Takabe, W., N. Jen, L. Ai, R. Hamilton, S. Wang, K. Holmes, F. Dharbandi, B. Khalsa, S. Bressler, and M. L. Barr. Oscillatory shear stress induces mitochondrial superoxide production: implication of NADPH oxidase and c-Jun NH2-terminal kinase signaling. Antioxid. Redox Signal. 15(5):1379, 2011.

    Article  Google Scholar 

  33. Tanaka, L. Y., L. R. G. Bechara, A. M. dos Santos, C. P. Jordão, L. G. O. de Sousa, T. Bartholomeu, L. I. Ventura, F. R. M. Laurindo, and P. R. Ramires. Exercise improves endothelial function: a local analysis of production of nitric oxide and reactive oxygen species. Nitric Oxide. 45:7–14, 2015.

    Article  Google Scholar 

  34. Thomas, S., S. Kotamraju, J. Zielonka, D. R. Harder, and B. Kalyanaraman. Hydrogen peroxide induces nitric oxide and proteosome activity in endothelial cells: a bell-shaped signaling response. Free Radic. Biol. Med. 42(7):1049–1061, 2007.

    Article  Google Scholar 

  35. Wang, Y. X., Y. Wang, S. Q. Li, U. R. A. Aziz, S. T. Liu, and K. R. Qin. The analysis of wall shear stress modulated by acute exercise in the human common carotid artery with an elastic tube model. Comput. Model. Eng. 116(2):127–147, 2018.

    Google Scholar 

  36. Wang, Y. X., C. Xiang, B. Liu, Y. Zhu, Y. Luan, S. T. Liu, and K. R. Qin. A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells. Biomed. Eng. Online 15(2):154, 2016.

    Article  Google Scholar 

  37. Yamamoto, K., and J. Ando. Endothelial cell and model membranes respond to shear stress by rapidly decreasing the order of their lipid phases. J. Cell Sci. 126(5):1227–1234, 2013.

    Article  Google Scholar 

  38. Zhang, J., and M. H. Friedman. Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude. Am. J. Physiol. Heart Circ. Physiol. 302(4):H983, 2012.

    Article  Google Scholar 

  39. Zhang, J., and M. H. Friedman. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency. Am. J. Physiol. Heart Circ. Physiol. 305(6):H894–H902, 2013.

    Article  Google Scholar 

  40. Zhou, J., Y. S. Li, and S. Chien. Shear stress-initiated signaling and its regulation of endothelial function significance. Arterioscler. Thromb. Vasc. Biol. 34(10):2191–2198, 2014.

    Article  Google Scholar 

Download references

Acknowledgments

The research described in this paper was supported in part by the National Natural Science Foundation of China (Grant Nos. 31370948, 11672065) and the Fundamental Research Funds for the Central Universities in China (Grant No. DUT18JC15).We would like to thank Prof. Wenyu Liu for kindly revising the manuscript.

Conflict of Interest

Yan-Xia Wang, Hai-Bin Liu, Peng-Song Li, Wen-Xue Yuan, Bo Liu, Shu-Tian Liu, Kai-Rong Qin declare no conflicts of interest.

Ethical Approval

All human subjects research was carried out in accordance with the Helsinki Declaration of 1975, as revised in 2000 (5) and approved by the Ethics Committee of Dalian University of Technology. No animal studies were carried out by the authors for this article.

Author information

Authors and Affiliations

  1. Department of Engineering Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian, 116024, China

    Yan-Xia Wang & Shu-Tian Liu

  2. School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian, 116024, China

    Kai-Rong Qin

  3. Department of Physical Education, Dalian University of Technology, Dalian, 116024, China

    Hai-Bin Liu, Peng-Song Li & Wen-Xue Yuan

  4. School of Biomedical Engineering, Dalian University of Technology, Dalian, 116024, China

    Hai-Bin Liu & Bo Liu

Authors
  1. Yan-Xia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hai-Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng-Song Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Xue Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shu-Tian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kai-Rong Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kai-Rong Qin.

Additional information

Associate Editor Jin-Yu Shao oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, YX., Liu, HB., Li, PS. et al. ROS and NO Dynamics in Endothelial Cells Exposed to Exercise-Induced Wall Shear Stress. Cel. Mol. Bioeng. 12, 107–120 (2019). https://doi.org/10.1007/s12195-018-00557-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-018-00557-w

Keywords

Search

Navigation