Background: Metabolic risk factors play a critical role in metabolic syndrome (MetS), and endothelial dysfunction is important in its development. On the other hand, Helicobacter pylori (H. pylori) infection has an essential role in MetS. The goal of present study was to evaluate the effect of H. pylori infection on endothelial dysfunction in MetS patients.

Methods: Based on the International Diabetes Federation (IDF) criteria, 80 MetS patients (59 females and 21 males, mean age: 48.94 ± 10.00 years) were selected. Plasma samples were assayed for H. pylori IgG using the ELISA method. Endothelial function was also evaluated by measuring plasma concentrations of endothelin-1 (ET- 1), E-selectin, and intracellular adhesion molecule (ICAM-1) using ELISA method. Also, NO2 −− and NO3 −− concentrations were measured by Griess method.

Results: Fifty patients (62.5%) had H. pylori infection. Plasma concentrations of ET-1, NO2−−, and NO3−− were significantly higher in MetS patients with positive H. pylori infection than in MetS patients with negative H. pylori infection (ET-1: 2.92 ± 2.33 vs 1.9 ± 1.4 pg/ml; P = 0.037; NO2 −−:19.46 ± 7/11 vs 15.46 ± 4.56 μM; P = 0.003; NO3 −−: 20.8 ± 10.53 vs 16.85 ± 6.03 μM, P = 0.036). However, plasma concentrations of ICAM-1 and E-selectin did not show any significant difference in the two groups.

Conclusion: The results showed a relationship between H. pylori infection and endothelial dysfunction. Helicobacter pylori infection can lead to atherosclerosis by causing chronic inflammation and affecting the factors contributing to the MetS.

metabolic syndrome, H. pylori, endothelial dysfunction

[2] Zamani, M., Ebrahimtabar, F., Zamani, V., Miller, W. H., Alizadeh-Navaei, R., Shokri- Shirvani, J., & Derakhshan, M. H. (2018). Systematic review with meta-analysis: The worldwide prevalence of Helicobacter pylori infection. Alimentary Pharmacology & Therapeutics, 47(7), 868–876. https://doi.org/10.1111/apt.14561

[3] Guclu, M., & Faruq Agan, A. (2017). Association of severity of Helicobacter pylori infection with peripheral blood neutrophil to lymphocyte ratio and mean platelet volume. Euroasian Journal of Hepato-Gastroenterology, 7(1), 11–16. https://doi.org/10.5005/jp-journals-10018-1204

[4] Vijayvergiya, R., & Vadivelu, R. (2015). Role of Helicobacter pylori infection in pathogenesis of atherosclerosis. World Journal of Cardiology, 7(3), 134–143. https://doi.org/10.4330/wjc.v7.i3.134

[5] Bokhari, A. S., Alshaya, M. M., Omar Badghaish, M. M., Albinissa, M. A., Al- Harbi, K. D., Almoghrabi, M. Y., . . .. (2018). Metabolic syndrome: Pathophysiology and treatment. The Egyptian Journal of Hospital Medicine, 70(8), 1388–1392. https://doi.org/10.12816/0044654

[6] Grundy, S. M. (2016). Metabolic syndrome update. Trends in Cardiovascular Medicine, 26(4), 364–373. https://doi.org/10.1016/j.tcm.2015.10.004

[7] Packard, R. R., & Libby, P. (2008). Inflammation in atherosclerosis: From vascular biology to biomarker discovery and risk prediction. Clinical Chemistry, 54(1), 24–38. https://doi.org/10.1373/clinchem.2007.097360

[8] Paulus, P., Jennewein, C., & Zacharowski, K. (2011). Biomarkers of endothelial dysfunction: Can they help us deciphering systemic inflammation and sepsis? Biomarkers, 16(sup1), S11–S21.

[9] Malerba, M., Nardin, M., Radaeli, A., Montuschi, P., Carpagnano, G. E., & Clini, E. (2017). The potential role of endothelial dysfunction and platelet activation in the development of thrombotic risk in COPD patients. Expert Review of Hematology, 10(9), 821–832. https://doi.org/10.1080/17474086.2017.1353416

[10] Aflyatumova, G. N., Nigmatullina, R. R., Sadykova, D. I., Chibireva, M. D., Fugetto, F., & Serra, R. (2018). Endothelin-1, nitric oxide, serotonin and high blood pressure in male adolescents. Vascular Health and Risk Management, 14, 213–223. https://doi.org/10.2147/VHRM.S170317

[11] Ando, T., Ishikawa, T., Takagi, T., Imamoto, E., Kishimoto, E., Okajima, A., Uchiyama, K., Handa, O., Yagi, N., Kokura, S., Naito, Y., Mizuno, S., Asakawa, A., Inui, A., & Yoshikawa, T. (2013). Impact of Helicobacter pylori eradication on circulating adiponectin in humans. Helicobacter, 18(2), 158–164. https://doi.org/10.1111/hel.12028

[12] Gen, R., Demir, M., & Ataseven, H. (2010). Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and low-grade inflammation. Southern Medical Journal, 103(3), 190–196. https://doi.org/10.1097/SMJ.0b013e3181cf373f

[13] Kim, H.-L., Chung, J., Kim, K.-J., Kim, H.-J., Seo, W.-W., Jeon, K.-H., Cho, I., Park, J. J., Lee, M. H., Suh, J., Lim, S. Y., Choi, S., & Kim, S. H. (2022). Lifestyle modification in the management of metabolic syndrome: statement from Korean Society of CardioMetabolic Syndrome (KSCMS). Korean Circulation Journal, 52(2), 93–109. https://doi.org/10.4070/kcj.2021.0328

[14] Grundy, S. M. (2008). Metabolic syndrome pandemic. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(4), 629–636. https://doi.org/10.1161/ATVBAHA.107.151092.

[15] Mozumdar, A., & Liguori, G. (2011). Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999-2006. Diabetes Care, 34(1), 216–219. https://doi.org/10.2337/dc10-0879

[16] Chen, T. P., Hung, H. F., Chen, M. K., Lai, H. H., Hsu, W. F., Huang, K. C., & Yang, K. C. (2015). Helicobacter pylori infection is positively associated with metabolic syndrome in Taiwanese adults: A cross-sectional study. Helicobacter, 20(3), 184–191. https://doi.org/10.1111/hel.12190

[17] Adachi, K., Mishiro, T., Toda, T., Kano, N., Fujihara, H., Mishima, Y., Konishi, A., Mochida, M., Takahashi, K., & Kinoshita, Y. (2018). Effects of Helicobacter pylori eradication on serum lipid levels. Journal of Clinical Biochemistry and Nutrition, 62, 264–269. https://doi.org/10.3164/jcbn.17-88

[18] Stępień, M., Stępień, A., Wlazeł, R. N., Paradowski, M., Banach, M., & Rysz, J. (2014). Obesity indices and inflammatory markers in obese non-diabetic normo-and hypertensive patients: A comparative pilot study. Lipids in Health and Disease, 13(1), 29. https://doi.org/10.1186/1476-511X-13-29

[19] Wondmkun, Y. T. (2020). Obesity, insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes, Metabolic Syndrome and Obesity, 13, 3611–3616. https://doi.org/10.2147/DMSO.S275898

[20] Asrih, M., & Jornayvaz, F. R. (2015). Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link? Molecular and Cellular Endocrinology, 418, 55–65. https://doi.org/10.1016/j.mce.2015.02.018

[21] Polyzos, S. A., Kountouras, J., Zavos, C., & Deretzi, G. (2011). The association between Helicobacter pylori infection and insulin resistance: A systematic review. Helicobacter, 16(2), 79–88. https://doi.org/10.1111/j.1523-5378.2011.00822.x

[22] Yan, Y.-Z., Ma, R.-L., Zhang, J.-Y., He, J., Ma, J.-L., Pang, H.-R., Mu, L.-T., Ding, Y.-S., Guo, H., Zhang, M., Liu, J.-M., Rui, D.-S., Wang, K., & Guo, S.-X. (2016). Association of insulin resistance with glucose and lipid metabolism: Ethnic heterogeneity in far Western China. Mediators of Inflammation. 2016.

[23] Moore, K. J., & Tabas, I. (2011). Macrophages in the pathogenesis of atherosclerosis. Cell, 145(3), 341–355. https://doi.org/10.1016/j.cell.2011.04.005

[24] Riad, M. (2021). Association of Helicobacter pylori infection with coronary artery disease: Is it an independent risk factor? The Egyptian Heart Journal, 73(1), 61. https://doi.org/10.1186/s43044-021-00185-2

[25] Upala, S., Jaruvongvanich, V., Riangwiwat, T., Jaruvongvanich, S., & Sanguankeo, A. (2016). Association between Helicobacter pylori infection and metabolic syndrome: A systematic review and meta-analysis. Journal of Digestive Diseases, 17(7), 433– 440. https://doi.org/10.1111/1751-2980.12367

[26] Kountouras, J., Papaefthymiou, A., Polyzos, S. A., Deretzi, G., Vardaka, E., Soteriades, E. S., Tzitiridou-Chatzopoulou, M., Gkolfakis, P., Karafyllidou, K., & Doulberis, M. (2021). Impact of Helicobacter pylori-related metabolic syndrome parameters on arterial hypertension. Microorganisms, 9(11), 2351. https://doi.org/10.3390/microorganisms9112351

[27] Mehu, M., Narasimhulu, C. A., & Singla, D. K. (2022). Inflammatory cells in atherosclerosis. Antioxidants, 11(2), 233. https://doi.org/10.3390/antiox11020233

[28] Zhao, W., Wu, C., & Chen, X. (2016). Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways. Cell Adhesion & Migration, 10(3), 248–258. https://doi.org/10.1080/19336918.2015.1119361

[29] Testerman, T. L., Semino-Mora, C., Cann, J. A., Qiang, B., Peña, E. A., Liu, H., Olsen, C. H., Chen, H., Appt, S. E., Kaplan, J. R., Register, T. C., Merrell, D. S., & Dubois, A. (2019). Both diet and Helicobacter pylori infection contribute to atherosclerosis in pre- and postmenopausal cynomolgus monkeys. PLoS One, 14(9), e0222001. https://doi.org/10.1371/journal.pone.0222001

[30] Cardillo, C., Mettimano, M., Mores, N., Koh, K. K., Campia, U., & Panza, J. A. (2004). Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators. Vascular Medicine, 9(3), 185–188. https://doi.org/10.1191/1358863x04vm546oa

[31] Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O. (2010). Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 107(41), 17716–17720. https://doi.org/10.1073/pnas.1008872107

[32] Aydemir, S., Eren, H., Tekin, I. O., Harmandar, F. A., Demircan, N., & Cabuk, M. (2010). Helicobacter pylori eradication lowers serum asymmetric dimethylarginine levels. Mediators of inflammation, 2010.

[33] Bourque, S. L., Davidge, S. T., & Adams, M. A. (2011). The interaction between endothelin-1 and nitric oxide in the vasculature: New perspectives. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 300(6), R1288– R1295. https://doi.org/10.1152/ajpregu.00397.2010

[34] Khimji, A. K., & Rockey, D. C. (2010). Endothelin—Biology and disease. Cellular Signalling, 22(11), 1615–1625. https://doi.org/10.1016/j.cellsig.2010.05.002