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Endothelial Cell Inflammatory Reactions Are Altered in the Presence of E-Cigarette Extracts of Variable Nicotine

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Exposure to tobacco smoke has been associated with heightened endothelial cell activities associated with cardiovascular diseases (CVD). Conversely, the exposure to nicotine both activates and inhibits particular endothelial cell functions. However, which constituent(s) of tobacco smoke is responsible for these changes is unknown, since toxic gases and fine particulate matter cannot be isolated. Electronic cigarette vapor allows us to isolate these constituents, providing us the ability to evaluate individual constituents. Here, we used e-cigarettes to (1) identify which constituents of tobacco products are most responsible for altered CVD functions and (2) elucidate the underlying risk of e-cigarette exposure. To accomplish this goal, endothelial cells were exposed to extracts produced from tobacco cigarettes or e-cigarettes. Endothelial cell inflammatory processes, viability, density and metabolic activity were observed. In general, a significant increase in complement deposition, the expression of the receptors for C1q, coupled with a decrease in cell proliferation and metabolic activity was observed. These results were independent of nicotine and the exposure to e-vapor was just as harmful as tobacco smoke extracts. Thus, the exposure to fine particulate matter and not toxic combustion gases or nicotine may be the most critical for regulating CVD progression.

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Receptor for the globular head of C1q


Receptor for the collagen region of C1q


  1. Benowitz, N. L., F. Kuyt, and P. Jacob, 3rd. Influence of nicotine on cardiovascular and hormonal effects of cigarette smoking. Clin. Pharmacol. Ther. 36:74–81, 1984.

    Article  Google Scholar 

  2. Cucina, A., V. Corvino, P. Sapienza, V. Borrelli, M. Lucarelli, S. Scarpa, R. Strom, L. Santoro-D’Angelo, and A. Cavallaro. Nicotine regulates basic fibroblastic growth factor and transforming growth factor beta1 production in endothelial cells. Biochem. Biophys. Res. Commun. 257:306–312, 1999.

    Article  Google Scholar 

  3. Czogala, J., M. L. Goniewicz, B. Fidelus, W. Zielinska-Danch, M. J. Travers, and A. Sobczak. Secondhand exposure to vapors from electronic cigarettes. Nicotine Tob. Res. 16:655–662, 2014.

    Article  Google Scholar 

  4. Fuoco, F. C., G. Buonanno, L. Stabile, and P. Vigo. Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes. Environ. Pollut. 184:523–529, 2014.

    Article  Google Scholar 

  5. Ghebrehiwet, B., J. Jesty, and E. I. Peerschke. Gc1q-r/p33: structure-function predictions from the crystal structure. Immunobiology 205:421–432, 2002.

    Article  Google Scholar 

  6. Ghebrehiwet, B., and E. I. Peerschke. Cc1q-r (calreticulin) and gc1q-r/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection. Mol. Immunol. 41:173–183, 2004.

    Article  Google Scholar 

  7. Goniewicz, M. L., J. Knysak, M. Gawron, L. Kosmider, A. Sobczak, J. Kurek, A. Prokopowicz, M. Jablonska-Czapla, C. Rosik-Dulewska, C. Havel, P. Jacob, 3rd, and N. Benowitz. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob. Control 23:133–139, 2014.

    Article  Google Scholar 

  8. Guarino, F., G. Cantarella, M. Caruso, C. Russo, S. Mancuso, G. Arcidiacono, R. R. Cacciola, R. Bernardini, and R. Polosa. Endothelial activation and injury by cigarette smoke exposure. J. Biol. Regul. Homeost. Agents 25:259–268, 2011.

    Google Scholar 

  9. Hom, S., L. Chen, T. Wang, B. Ghebrehiwet, W. Yin, and D. A. Rubenstein. Platelet activation, adhesion, inflammation and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentration. Platelets in press.

  10. Maria, Z., W. Yin, and D. A. Rubenstein. Glycated albumin and pathological shear stress alters endothelial cell thrombogenic potential, pro-inflammatory state and cytoskeletal dynamics. J. Diabetes Metab. S4:003, 2011.

    Google Scholar 

  11. Maria, Z., W. Yin, and D. A. Rubenstein. Combined effects of physiologically relevant disturbed wall shear stress and glycated albumin on endothelial cell functions associated with inflammation, thrombosis and cytoskeletal dynamics. J. Diabetes Investig. 5:372–381, 2014.

    Article  Google Scholar 

  12. Morris, P. B., B. A. Ference, E. Jahangir, D. N. Feldman, J. J. Ryan, H. Bahrami, M. F. El-Chami, S. Bhakta, D. E. Winchester, M. H. Al-Mallah, M. S. Shields, P. Deedwania, L. S. Mehta, B. A. Phan, and N. L. Benowitz. Cardiovascular effects of exposure to cigarette smoke and electronic cigarettes: clinical perspectives from the prevention of cardiovascular disease section leadership council and early career councils of the American College of Cardiology. J. Am. Coll. Cardiol. 66:1378–1391, 2015.

    Article  Google Scholar 

  13. Patil, A. J., A. L. Gramajo, A. Sharma, G. M. Seigel, B. D. Kuppermann, and M. C. Kenney. Differential effects of nicotine on retinal and vascular cells in vitro. Toxicology 259:69–76, 2009.

    Article  Google Scholar 

  14. Peerschke, E. I., A. S. Bayer, B. Ghebrehiwet, and Y. Q. Xiong. Gc1qr/p33 blockade reduces staphylococcus aureus colonization of target tissues in an animal model of infective endocarditis. Infect. Immun. 74:4418–4423, 2006.

    Article  Google Scholar 

  15. Peerschke, E. I., J. O. Minta, S. Z. Zhou, A. Bini, A. Gotlieb, R. W. Colman, and B. Ghebrehiwet. Expression of gc1q-r/p33 and its major ligands in human atherosclerotic lesions. Mol. Immunol. 41:759–766, 2004.

    Article  Google Scholar 

  16. Peerschke, E. I., W. Yin, and B. Ghebrehiwet. Platelet mediated complement activation. Adv. Exp. Med. Biol. 632:81–91, 2008.

    Google Scholar 

  17. Pereira, I. A., and E. F. Borba. The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of atherosclerosis. Swiss Med. Wkly. 138:534–539, 2008.

    Google Scholar 

  18. Robbins, R. A., K. J. Nelson, G. L. Gossman, S. Koyama, and S. I. Rennard. Complement activation by cigarette smoke. Am. J. Physiol. 260:L254–L259, 1991.

    Google Scholar 

  19. Rubenstein, D., D. Han, S. Goldgraben, H. El-Gendi, P. I. Gouma, and M. D. Frame. Bioassay chamber for angiogenesis with perfused explanted arteries and electrospun scaffolding. Microcirculation 14:723–737, 2007.

    Article  Google Scholar 

  20. Rubenstein, D. A., S. Hom, B. Ghebrehiwet, and W. Yin. Tobacco and e-cigarette products initiate kupffer cell inflammatory responses. Mol. Immunol. 67:652–660, 2015.

    Article  Google Scholar 

  21. Rubenstein, D., J. Jesty, and D. Bluestein. Differences between mainstream and sidestream cigarette smoke extracts and nicotine in the activation of platelets under static and flow conditions. Circulation 109:78–83, 2004.

    Article  Google Scholar 

  22. Rubenstein, D. A., B. E. Morton, and W. Yin. The combined effects of sidestream smoke extracts and glycated serum albumin on endothelial cells and platelets. Cardiovasc. Diabetol. 9:28, 2010.

    Article  Google Scholar 

  23. Schmitt, M. M., L. Fraemohs, T. M. Hackeng, C. Weber, and R. R. Koenen. Atherogenic mononuclear cell recruitment is facilitated by oxidized lipoprotein-induced endothelial junctional adhesion molecule-a redistribution. Atherosclerosis 234:254–264, 2014.

    Article  Google Scholar 

  24. Schulte, D. J., A. Yilmaz, K. Shimada, M. C. Fishbein, E. L. Lowe, S. Chen, M. Wong, T. M. Doherty, T. Lehman, T. R. Crother, R. Sorrentino, and M. Arditi. Involvement of innate and adaptive immunity in a murine model of coronary arteritis mimicking kawasaki disease. J. Immunol. 183:5311–5318, 2009.

    Article  Google Scholar 

  25. Yang, Y. M., and G. T. Liu. Damaging effect of cigarette smoke extract on primary cultured human umbilical vein endothelial cells and its mechanism. Biomed. Environ. Sci. 17:121–134, 2004.

    Google Scholar 

  26. Yin, W., B. Ghebrehiwet, B. Weksler, and E. I. Peerschke. Regulated complement deposition on the surface of human endothelial cells: effect of tobacco smoke and shear stress. Thromb. Res. 122:221–228, 2008.

    Article  Google Scholar 

  27. Yin, W., E. C. Ngwe, B. Ghebrehiwet, and D. A. Rubenstein. The combined effect of sidestream smoke and dynamic shear stress on endothelial cell inflammatory responses. Thromb. Res. 135:362–367, 2015.

    Article  Google Scholar 

  28. Yin, W., and D. A. Rubenstein. Dose effect of shear stress on platelet complement activation in a cone and plate shearing device. Cell. Mol. Bioeng. 2:274–280, 2009.

    Article  Google Scholar 

  29. Yin, W., and D. A. Rubenstein. Differences between mainstream and sidestream tobacco smoke extracts and nicotine in the activation and aggregation of platelets subjected to cardiovascular conditions in diabetes. Diabetes Vasc. Dis. Res. 10:57–64, 2013.

    Article  Google Scholar 

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Conflict of interest

Dr. Rubenstein, Ms. Barber, Dr. Yin and Dr. Ghebrehiwet report no conflict of interest.

Ethical Considerations

All authors have read and approved the submission of this manuscript and have agreed to be named as authors. Additionally, each author has contributed significantly to the work presented, by designing the experiments, conducting the experiments, analyzing/summarizing the results and/or critically analyzing the manuscript. All work of others has been properly acknowledged. All data are true and accurate to the knowledge of the authors. None of the authors have any potential competing interest with the publication of this manuscript. This manuscript is not under consideration for publication in any other journal and has not been previously published in any other format and is original. This work does not involve human subjects, vertebrae animals, human embryonic stem cells and only makes use of cell obtained commercially, thus it was not necessary for our local IRB/IACUC to review/approve this work.

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Correspondence to David A. Rubenstein.

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Associate Editor Cheng Dong oversaw the review of this article.

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Barber, K.E., Ghebrehiwet, B., Yin, W. et al. Endothelial Cell Inflammatory Reactions Are Altered in the Presence of E-Cigarette Extracts of Variable Nicotine. Cel. Mol. Bioeng. 10, 124–133 (2017).

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