Advertisement

Human Physiology

, Volume 45, Issue 5, pp 543–551 | Cite as

Prognostic Importance of Systemic Endotoxinemia Indicators in Atherogenesis

  • D. P. PokusaevaEmail author
  • I. A. Anikhovskaya
  • L. A. Korobkova
  • G. G. Enukidze
  • M. Yu. Yakovlev
Article
  • 4 Downloads

Abstract

Numerous studies have indicated a close relationship between lipid metabolism disorders and the inflammatory component of atherogenesis. Excess endotoxin (ET) in the general circulation can induce chronic inflammation, and its role in atherogenesis is difficult to overestimate. The involvement of lipopolysaccharide (LPS) in atherogenesis in humans has been studied without assessing the morphological changes in the structure of the vascular wall. It seemed therefore of importance to study the dynamics of the systemic endotoxinemia (SEE) parameters as probable markers of atherosclerosis in association with a progression of morphological changes in the arterial wall. A total of 104 volunteers were examined. The patients had lipid profile abnormalities without clinical manifestations of atherosclerosis, reported themselves to be healthy, and belonged to the moderate risk category (2–4%) on the SCORE scale. A Control group (n = 9) comparable the patients by sex and age. All subjects underwent a duplex scanning of extracranial brachiocephalic arteries (BCA) and a venous blood testing for lipid profile and SEE parameters, including ET, antibodies to the hydrophobic and hydrophilic part of the LPS molecule, and their concentration ratio. The patients were divided into three groups based on the structural changes detected in the arterial wall by ultrasound testing: no morphological change in the BCA (Normal), a thickening of the intima–media complex (TIM), and identified atherosclerotic plaque (ASP). Patients of the ASP group have a significantly higher ET concentration and a reduced activity of anti-ET immunity (AEI) as compared with the accepted reference values and values observed in the TIM group. ET level was not increased, but the AEI activity was reduced in the TIM group, as well as in the Control group. All SEE parameters were within their normal ranges in the Normal group. The main risk factors in assessing the risk for detecting atherosclerotic plaque of the BCA were an age over 55 years and a decrease in antibodies to the hydrophobic part of the LPS molecule below 163 c. u. o. d. Significant differences observed in SEE parameters between patient groups made it possible to assume that an increase in blood LPS concentration and a decrease in AEI activity are risk factors for atherosclerosis.

Keywords:

systemic endotoxinemia atherogenesis atherosclerosis endotoxin risk factors inflammation lipopolysaccharide anti-endotoxin immunity cholesterol lipid profile 

Notes

COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interests. The authors declare that they have no real or potential conflict of interest with respect to publication of this article.

Statement of compliance with standards of research involving humans as subjects. All studies were in accordance with the biomedical ethical standards of the 1964 Helsinki Declaration and its later amendments and were approved by the Local Ethics Committee at the Institute of General Pathology and Pathophysiology (Moscow). All participants voluntarily gave their written informed consent for participation after being informed about potential risks and benefits and the study procedure.

REFERENCES

  1. 1.
    Wu, M.Y., Li, C.J., Hou, M.F., and Chu, P.Y., New insights into the role of inflammation in the pathogenesis of atherosclerosis, Int. J. Mol. Sci., 2017, vol. 18, no. 10, p. 2034.CrossRefGoogle Scholar
  2. 2.
    Anderson, T.J., Gregoire, J., Hegele, R.A., et al., 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult, Can. J. Cardiol., 2013, vol. 29, no. 2, p. 151.CrossRefGoogle Scholar
  3. 3.
    El Harchaoui, K., van der Steeg, W.A., Stroes, E.S., et al., Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women. The EPIC-Norfolk prospective population study, J. Am. Coll. Cardiol., 2007, vol. 49, no. 5, p. 547.CrossRefGoogle Scholar
  4. 4.
    Salakhov, I.M., Anikhovskaya, I.A., Maiskii, I.A., et al., The normative data of systemic endotoxinemia as the basic element of role definition of lipopolysaccharides of gut organisms in general pathology, Patogenez, 2015, vol. 13, no. 1, p. 18.Google Scholar
  5. 5.
    Findlay, L., Desai, T., Heath, A., et al., Collaborative study for the establishment of the WHO 3(rd) International Standard for Endotoxin, the Ph. Eur. endotoxin biological reference preparation batch 5 and the USP Reference Standard for Endotoxin Lot H0K354, Pharm. Biol. Sci. Notes, 2015, vol. 2015, p. 73.Google Scholar
  6. 6.
    Yakovlev, M.Yu., Intestinal endotoxin and inflammation, in Dermatovenerologiya. Natsional’noe rukovodstvo (Dermatovenereology: National Guide), Moscow: GEOTAR-Media, 2013, ch. 8, p. 70.Google Scholar
  7. 7.
    Rittig, N., Thomsen, H.H., Bach, E., et al., Hormone and cytokine responses to repeated endotoxin exposures-no evidence of endotoxin tolerance after 5 weeks in humans, Shock, 2015, vol. 44, no. 1, p. 32.CrossRefGoogle Scholar
  8. 8.
    Swann, J.R., Want, E.J., Geier, F.M., et al., Systemic gut microbial modulation of bile acid metabolism in host tissue compartments, Proc. Natl. Acad. Sci. U.S.A., 2011, vol. 108, no. 1, p. 4523.CrossRefGoogle Scholar
  9. 9.
    Battson, M.L., Lee, D.M., Weir, T.L., and Gentile, C.L., The gut microbiota as a novel regulator of cardiovascular function and disease, J. Nutr. Biochem., 2018, vol. 56, p. 1.CrossRefGoogle Scholar
  10. 10.
    Wu, P., Jia, F., Zhang, B., and Zhang, P., Risk of cardiovascular disease in inflammatory bowel disease, J. Exp. Ther. Med., 2017, vol. 13, no. 2, p. 395.CrossRefGoogle Scholar
  11. 11.
    Pokusaeva, D.P., The influence mechanism of systemic endotoxemia on the development and course of atherosclerosis at the cellular, systemic, and organismic levels, Patogenez, 2018, vol. 6, no. 2, p. 12.Google Scholar
  12. 12.
    Okorokov, P.L., Anychovskaya, I.A., Yakovleva, M.M., et al., Nutritional factors of inflammation induction or lipid mechanism of endotoxin transport, Hum. Physiol., 2012, vol. 38, no. 6, p. 649.CrossRefGoogle Scholar
  13. 13.
    Horseman, M.A., Surani, S., and Bowman, J.D., Endotoxin, toll-like receptor-4, and atherosclerotic heart disease, Curr. Cardiol. Rev., 2017, vol. 13, no. 2, p. 86.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Li, J., Lin, S., Vanhoutte, P.M., et al., Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe –/– mice, Circulation, 2016, vol. 133, no. 24, p. 2434.CrossRefGoogle Scholar
  15. 15.
    Singh, S., Singh, H., Loftus, E.V., and Pardi, D.S., Risk of cerebrovascular accidents and ischemic heart disease in patients with inflammatory bowel disease: a systematic review and meta-analysis, Clin. Gastroenterol. Hepatol., 2014, vol. 12, no. 3, p. 382.CrossRefGoogle Scholar
  16. 16.
    Geng, S., Yuan, R., and Li, L., Chronic polarization of inflammatory monocytes by super-low grade endotoxin aggravates the pathogenesis of atherosclerosis, Circulation, 2017, vol. 136, no. 1, p. A20934.Google Scholar
  17. 17.
    Yakovlev, M.Yu., Endotoxin shock, Kazan. Med. Zh., 1987, vol. 68, no. 3, p. 207.Google Scholar
  18. 18.
    Jiang, D., Yang, Y., and Li, D., Lipopolysaccharide induced vascular smooth muscle cells proliferation: A new potential therapeutic target for proliferative vascular diseases, J. Cell Prolif., 2017, vol. 50, no. 2, p. e12332.CrossRefGoogle Scholar
  19. 19.
    Anikhovskaya, I.A., Kubatiev, A.A., and Yakovlev, M.Yu., Endotoxin theory of atherosclerosis, Hum. Physiol., 2015, vol. 41, no. 1, p. 89.CrossRefGoogle Scholar
  20. 20.
    Chizhikov, N.V., Likhoded, V.G., Svetukhin, A.M., and Yakovlev, M.Yu., Endotoksin kishechnoi mikroflory v klinike i patogeneze khronicheskoi ishemii nizhnikh konechnostei (Endotoxin of Intestinal Microflora in Clinic and Pathogenesis of Chronic Lower Limb Ischemia), Penza: Penz. Gos. Pedagog. Univ. im. V.G. Belinskogo, 2002.Google Scholar
  21. 21.
    Anikhovskaya, I.A., Kubatiev, A.A., Salakhov, I.M., et al., Dynamics of endotoxin concentration in blood serum in patients with acute uncomplicated Q-myocardial infarction, Patol. Fiziol. Eksp. Ter., 2015, vol. 59, no. 3, p. 55.Google Scholar
  22. 22.
    Stock, J., Gut microbiota: an environmental risk factor for cardiovascular disease, Atherosclerosis, 2013, vol. 229, no. 2, p. 440.CrossRefGoogle Scholar
  23. 23.
    Diks, S.H., van Deventer, S.J.H., and Peppelenbosch, M.P., Lipopolysaccharide recognition, internalisation, signalling and other cellular effects, J. Endotoxin Res., 2001, vol. 7, no. 5, p. 335.PubMedGoogle Scholar
  24. 24.
    Trebicka, E., Jacob, S., Pirzai, W., et al., Role of antilipopolysaccharide antibodies in serum bactericidal activity against Salmonella enterica serovar Typhimurium in healthy adults and children in the United States, Clin. Vaccine Immunol., 2013, vol. 20, no. 10, p. 1491.CrossRefGoogle Scholar
  25. 25.
    Poxton, I.R., Antibodies to lipopolysaccharide, J. Immunol. Methods, 1995, vol. 186, no. 1, p. 1.CrossRefGoogle Scholar
  26. 26.
    Likhoded, V.G., Bondarenko, V.M., and Gintsburg, A.L., Receptor theory of atherosclerosis, Vestn. Ross. Akad. Med. Nauk, 2010, no. 5, p. 11.Google Scholar
  27. 27.
    Lehr, H.A., Sagban, T.A., Ihling, C., et al., Immunopathogenesis of atherosclerosis, Circulation, 2001, vol. 104, no. 8, p. 914.CrossRefGoogle Scholar
  28. 28.
    Neves, A.L., Coelho, J., Couto, L., et al., Metabolic endotoxemia: a molecular link between obesity and cardiovascular disease, J. Mol. Endocrinol., 2013, vol. 51, no. 2, p. R51.CrossRefGoogle Scholar
  29. 29.
    Pokusaeva, D.P., Anikhovskaya, I.A., Korobkova, L.A., and Yakovlev, M.Yu., Correlations of indices of systemic endotoxinemia with lipid profile in patients without clinical manifestation of atherosclerosis, Patogenez, 2018, vol. 16, no. 4, p. 182.Google Scholar
  30. 30.
    Peng, J., Luo, F., Ruan, G., et al., Hypertriglyceridemia and atherosclerosis, Lipids Health Dis., 2017, vol. 16, no. 1, p. 233.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • D. P. Pokusaeva
    • 1
    • 2
    Email author
  • I. A. Anikhovskaya
    • 1
    • 2
  • L. A. Korobkova
    • 3
  • G. G. Enukidze
    • 2
  • M. Yu. Yakovlev
    • 1
    • 2
    • 4
  1. 1.Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Clinical Diagnostic Society, Clinics of Institute of General Pathology and PathophysiologyMoscowRussia
  3. 3.Skolkovo Institute of Science and TechnologyMoscowRussia
  4. 4.Pirogov Russian National Research Medical University, Ministry of Health of the Russian FederationMoscowRussia

Personalised recommendations