ROS and NO Dynamics in Endothelial Cells Exposed to Exercise-Induced Wall Shear Stress
- 26 Downloads
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.
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.
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.
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.
KeywordsExercise Wall shear stress (WSS) Reactive oxygen species (ROS) Nitric oxide (NO) Endothelial cells
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.
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.
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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
- 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.CrossRefGoogle 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.CrossRefGoogle 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