Skip to main content
SpringerLink
Log in

Laminar Shear Stress Promotes Nicotine-Induced Inflammation and Hemostatic Expression in Human Endothelial Cells

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

Abstract

Nicotine has been known to play a pathogenic role in various cardiovascular disorders. However, the definite mechanism of nicotine-mediated endothelial dysfunction in vivo remains unclear because hemodynamic factor in most of in vitro studies was excluded. In this study, we investigated how nicotine affects human umbilical vein endothelial cells (HUVECs), from views of inflammatory and hemostatic responses of the cells, under a hemodynamic environment as occurred in vivo. Our results showed that both inflammation, reflected by production of reactive oxygen species and efficacy of monocytes adhesion, and hemostatic expression of HUVECs were abnormally enhanced after treated with 10−4 M nicotine and 12 dynes cm−2 laminar shear stress (LSS) simultaneously for 24 h, and that the protein expression levels of VCAM-1, ICAM-1, and PAI-1 were significantly enhanced 1.3-, 2- and 2-fold (p < 0.05 for each), respectively, as compared to the group with nicotine alone; 2.2-, 3- and 4.2-fold (p < 0.05 for each), respectively, as compared to the group with LSS alone. We reasoned that those irregular expressions were resulted from the reduction of endothelial nitric oxide synthase that was initially caused by nicotine exposure and exacerbated due to LSS treatment. Furthermore, all the impaired responses can be alleviated by use of 1 μg mL−1 recombinant tissue plasminogen activator, implicating that the irregular inflammation may be due to thrombosis.

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

Similar content being viewed by others

References

  1. Aboyans, V., P. Lacroix, and M. H. Criqui. Large and small vessels atherosclerosis: similarities and differences. Prog. Cardiovasc. Dis. 50:112–125, 2007.

    Article  Google Scholar 

  2. Albaugh, G., E. Bellavance, L. Strande, S. Heinburger, C. W. Hewitt, and J. B. Alexander. Nicotine induces mononuclear leukocyte adhesion and expression of adhesion molecules, VCAM and ICAM, in endothelial cells in vitro. Ann. Vasc. Surg. 18:302–307, 2004.

    Article  Google Scholar 

  3. Boon, R. A., E. Hergenreider, and S. Dimmeler. Atheroprotective mechanisms of shear stress-regulated microRNAs. Thromb. Haemost. 108:616–620, 2012.

    Article  Google Scholar 

  4. Casas, J. P., L. E. Bautista, S. E. Humphries, and A. D. Hingorani. Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects. Circulation 109:1359–1365, 2004.

    Article  Google Scholar 

  5. Cunningham, K. S., and A. I. Gotlieb. The role of shear stress in the pathogenesis of atherosclerosis. Lab. Invest. 85:9–23, 2005.

    Article  Google Scholar 

  6. Devaraj, S., D. Y. Xu, and I. Jialal. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 107:398–404, 2003.

    Article  Google Scholar 

  7. Diehm, N., A. Shang, A. Silvestro, D. D. Do, F. Dick, J. Schmidli, F. Mahler, and I. Baumgartner. Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty. Eur. J. Vasc. Endovasc. Surg. 31:59–63, 2006.

    Article  Google Scholar 

  8. Duffy, M. J., P. M. McGowan, and W. M. Gallagher. Cancer invasion and metastasis: changing views. J. Pathol. 214:283–293, 2008.

    Article  Google Scholar 

  9. Endemann, D. H., and E. L. Schiffrin. Endothelial dysfunction. J. Am. Soc. Nephrol. 15:1983–1992, 2004.

    Article  Google Scholar 

  10. Fahim, M. A., A. Nemmar, S. Al-Salam, S. Dhanasekaran, M. Shafiullah, J. Yasin, and M. Y. Hassan. Thromboembolic injury and systemic toxicity induced by nicotine in mice. Gen. Physiol. Biophys. 33:345–355, 2014.

    Article  Google Scholar 

  11. Ghosh, A. K., and D. E. Vaughan. PAI-1 in tissue fibrosis. J. Cell Physiol. 227:493–507, 2012.

    Article  Google Scholar 

  12. Griendling, K. K., and G. A. FitzGerald. Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108:1912–1916, 2003.

    Article  Google Scholar 

  13. Hadad, N., L. Tuval, V. Elgazar-Carmom, R. Levy, and R. Levy. Endothelial ICAM-1 protein induction is regulated by cytosolic phospholipase A2α via both NF-κB and CREB transcription factors. J. Immunol. 186:1816–1827, 2011.

    Article  Google Scholar 

  14. Haltmayer, M., T. Mueller, W. Horvath, C. Luft, W. Poelz, and D. Haidinger. Impact of atherosclerotic risk factors on the anatomical distribution of peripheral arterial disease. Int. Angiol. 20:200–207, 2001.

    Google Scholar 

  15. Heeschen, C., J. J. Jang, M. Weis, A. Pathak, S. Kaji, R. S. Hu, P. S. Tsao, F. L. Johnson, and J. P. Cooke. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat. Med. 7:833–839, 2001.

    Article  Google Scholar 

  16. Khan, B. V., D. G. Harrison, M. T. Olbrych, R. W. Alexander, and R. M. Medford. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc. Natl. Acad. Sci. USA 93:9114–9119, 1996.

    Article  Google Scholar 

  17. Koppenol, W. H., J. J. Moreno, W. A. Pryor, H. Ischiropoulos, and J. S. Beckman. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem. Res. Toxicol. 5:834–842, 1992.

    Article  Google Scholar 

  18. Lee, Y. H., R. S. Chen, N. C. Chang, K. R. Lee, C. T. Huang, Y. C. Huang, and F. M. Ho. Synergistic impact of nicotine and shear stress induces cytoskeleton collapse and apoptosis in endothelial cells. Ann. Biomed. Eng. 43:2220–2230, 2015.

    Article  Google Scholar 

  19. Lee, J., and J. P. Cooke. The role of nicotine in the pathogenesis of atherosclerosis. Atherosclerosis 215:281–283, 2011.

    Article  Google Scholar 

  20. Lindenblatt, N., U. Platz, J. Hameister, E. Klar, M. D. Menger, and B. Vollmar. Distinct effects of acute and chronic nicotine application on microvascular thrombus formation and endothelial function in male and female mice. Langenbecks. Arch. Surg. 392:285–295, 2007.

    Article  Google Scholar 

  21. Liu, Y., Y. Zhu, F. Rannou, T. S. Lee, K. Formentin, L. Zeng, X. Yuan, N. Wang, S. Chien, B. N. Forman, and J. Y. Shyy. Laminar flow activates peroxisome proliferator-activated receptor-gamma in vascular endothelial cells. Circulation 110:1128–1133, 2004.

    Article  Google Scholar 

  22. Lum, H., and K. A. Roebuck. Oxidant stress and endothelial cell dysfunction. Am. J. Physiol. Cell. Physiol. 280:C719–741, 2001.

    Google Scholar 

  23. Malek, A. M., S. L. Alper, and S. Izumo. Hemodynamic shear stress and its role in atherosclerosis. J. Am. Med. Assoc. 282:2035–2042, 1999.

    Article  Google Scholar 

  24. Milstien, S., and Z. Katusic. Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Biochem. Biophys. Res. Commun. 263:681–684, 1999.

    Article  Google Scholar 

  25. Nagel, T., N. Resnick, C. F. Dewey, Jr, and M. A. Gimbrone, Jr. Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler. Thromb. Vasc. Biol. 19:1825–1834, 1999.

    Article  Google Scholar 

  26. Narayanaswami, V., S. S. Somkuwar, D. B. Horton, L. A. Cassis, and L. P. Dwoskin. Angiotensin AT1 and AT2 receptor antagonists modulate nicotine-evoked [3H] dopamine and [3H] norepinephrine release. Biochem. Pharmacol. 86:656–665, 2013.

    Article  Google Scholar 

  27. Ni, C. W., H. J. Hsieh, Y. J. Chao, and D. L. Wang. Shear flow attenuates serum-induced STAT3 activation in endothelial cells. J. Biol. Chem. 278:19702–19708, 2003.

    Article  Google Scholar 

  28. Papaioannou, T. G., and C. Stefanadis. Vascular wall shear stress: basic principles and methods. Hellenic. J. Cardiol. 46:9–15, 2005.

    Google Scholar 

  29. Rodella, L. F., C. Rossini, G. Favero, E. Foglio, C. Loreto, and R. Rezzani. Nicotine-induced morphological changes in rat aorta: the protective role of melatonin. Cells Tissues Organs. 195:252–259, 2012.

    Article  Google Scholar 

  30. Sackett, D. L., R. W. Gibson, I. D. Bross, and J. W. Pickren. Relation between aortic atherosclerosis and the use of cigarettes and alcohol. An autopsy study. N. Engl. J. Med. 279:1413–1420, 1968.

    Article  Google Scholar 

  31. Smith, F. B., A. J. Lee, F. G. Fowkes, A. Rumley, and G. D. Lowe. Smoking, haemostatic factors and the severity of aorto-iliac and femoro-popliteal disease. Thromb. Haemost. 75:19–24, 1996.

    Google Scholar 

  32. Takabe, W., E. Warabi, and N. Noguchi. Anti-atherogenic effect of laminar shear stress via Nrf2 activation. Antioxid. Redox. Signal. 15:1415–1426, 2011.

    Article  Google Scholar 

  33. Tonnessen, B. H., S. R. Severson, R. D. Hurt, and V. M. Miller. Modulation of nitric-oxide synthase by nicotine. J. Pharmacol. Exp. Ther. 295:601–606, 2000.

    Google Scholar 

  34. Traub, O., and B. Berk. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler. Thromb. 18:677–685, 1998.

    Article  Google Scholar 

  35. van Buul, J. D., C. Voermans, V. van den Berg, E. C. Anthony, F. P. Mul, S. van Wetering, C. E. van der Schoot, and P. L. Hordijk. Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin. J. Immunol. 168:588–596, 2002.

    Article  Google Scholar 

  36. Vaughan, D. E. PAI-1 and atherothrombosis. J. Thromb. Haemost. 3:1879–1883, 2005.

    Article  Google Scholar 

  37. Virdis, A., U. Dell’Agnello, and S. Taddei. Impact of inflammation on vascular disease in hypertension. Maturitas. 78:179–183, 2014.

    Article  Google Scholar 

  38. Wang, W., C. H. Ha, B. S. Jhun, C. Wong, M. K. Jain, and Z. G. Jin. Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood. 115:2971–2979, 2010.

    Article  Google Scholar 

  39. Xu, M., J. E. Scott, K. Z. Liu, H. R. Bishop, D. E. Renaud, R. M. Palmer, A. Soussi-Gounni, and D. A. Scott. The influence of nicotine on granulocytic differentiation—inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release. BMC Cell Biol. 9:19, 2008.

    Article  Google Scholar 

  40. Zarins, C. K., M. A. Zatina, D. P. Giddens, D. N. Ku, and S. Glagov. Shear stress regulation of artery lumen diameter in experimental atherogenesis. J. Vasc. Surg. 5:413–420, 1987.

    Article  Google Scholar 

  41. Zhang, S., I. Day, and S. Ye. Nicotine induced changes in gene expression by human coronary artery endothelial cells. Atherosclerosis. 154:277–283, 2001.

    Article  Google Scholar 

  42. Zhou, X., Y. Sheng, R. Yang, and X. Kong. Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression. Cardiology. 115:243–250, 2010.

    Article  Google Scholar 

  43. Zidovetzki, R., P. Chen, M. Fisher, F. M. Hofman, and F. M. Faraci. Nicotine increases plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-associated pathway. Stroke 30:651–655, 1999.

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported by Ministry of Science and Technology, R.O.C. (MOST 104-2221-E-008-095; Y.-H. Lee).

Conflict of interest

Yu-Hsiang Lee, Chi-Chung Lee, Chien-Hsun Huang, and Feng-Ming Ho declare no conflict of interest.

Ethical Standards

The authors for this article carried out no human studies. The authors for this article carried out no animal studies.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences and Engineering, National Central University, No. 300, Jhongda Rd., Taoyuan City, 32001, Taiwan, R.O.C

    Yu-Hsiang Lee & Chi-Chung Lee

  2. Department of Obstetrics and Gynecology, Tao-Yuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan, R.O.C.

    Chien-Hsun Huang

  3. Department of Internal Medicine, Tao-Yuan General Hospital, Ministry of Health and Welfare, No. 1492 Chung-Shan Rd., Taoyuan City, 33004, Taiwan, R.O.C.

    Feng-Ming Ho

  4. Department of Chemical Engineering, R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan City, Taiwan, R.O.C.

    Feng-Ming Ho

  5. Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei City, Taiwan, R.O.C.

    Feng-Ming Ho

Authors
  1. Yu-Hsiang Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chi-Chung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chien-Hsun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Feng-Ming Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yu-Hsiang Lee or Feng-Ming Ho.

Additional information

Associate Editor Joyce Wong 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

Lee, YH., Lee, CC., Huang, CH. et al. Laminar Shear Stress Promotes Nicotine-Induced Inflammation and Hemostatic Expression in Human Endothelial Cells. Cel. Mol. Bioeng. 9, 466–477 (2016). https://doi.org/10.1007/s12195-016-0434-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-016-0434-y

Keywords

Search

Navigation