DOI: https://doi.org/None

Kashukh Ye.A., Ivashkin V.T.

In the presented review a new potential risk factor for atherosclerosis and cardiovascular disease such as microflora of the human gastrointestinal tract is considered. The modern concept of lipid metabolism and its effects on human health outlining the basic theory of atherosclerosis development in a historical context is described in detail. The data about inflammatory proteins produced by oral cavity bacteria and contributing to the development of atherosclerosis as well as the damage of myocardium are provided. Particular attention is given to the small intestine microflora metabolism and its participation in the acceleration of the development of atherosclerosis. Convincing evidence of the impact of intestinal bacteria on such important factors of the cardiovascular risk, as obesity, metabolic syndrome, dyslipidemia are shown. There are also described presently known such proatherogenic molecules as trimethylamine-N-oxide and gamma-butyrobetaine. Their connection with the protracted cardiovascular risk, potential pathways and mechanisms of these molecules formation involving intestinal microflora is presented. Substances serving as precursors of proatherogenic molecules are described and their role in nutrition is obtained. Finally there is presented information about association of trimethylamine-N-oxide with increased angiotensin II concentrations and the development of hypertension and chronic heart failure.
atherosclerosis, cardiovascular disease, microbiome, arterial hypertension trimethylamine-N-oxide, trimethylamine

Список литературы: 
  1. Mendis S., Davis S., Norrving B. Organizational Update: The World Health Organization Global Status Report on Noncommunicable Diseases. 2014; One More Landmark Step in the Combat Against Stroke and Vascular Diseas. Stroke. 2015; 46: 121–2.
  2. Ettinger G., MacDonald K., Reid G., Burton J.P. The influence of the human microbiome and probiotics on cardiovascular health. Gut Microbes. 2014; 5 (6): 719–28.
  3. Rafieian-Kopaei M., Setorki M., Doudi M., Baradaran A., Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int. J. Prev. Med. 2014; 5 (8): 927–46.
  4. Dewhirst F.E., Chen T., Izard J., Paster B.J., Tanner A.C., Yu W.H., Lakshmanan A., Wade W.G. The human oral microbiome. J. Bacteriol. 2010; 192: 5002–17.
  5. Marsh P. Role of the oral microflora in health. Microb. Ecol. Health Dis. 2000; 12: 130–7.
  6. Marijon E., Mirabel M., Celermajer D.S., Jouven X. Rheumatic heart disease. Lancet. 2012; 379: 953–64.
  7. Mustapha I.Z., Debrey S., Oladubu M., Ugarte R. Markers of systemic bacterial exposure in periodontaldisease and cardiovascular disease risk: A systematicreview and meta-analysis. J. Periodontol. 2007; 78: 2289–302.
  8. Teles R., Wang C.Y. Mechanisms involved in the associationbetween periodontal diseases and cardiovasculardisease. Oral Dis. 2011; 17: 450–61.
  9. Haraszthy V.I., Zambon J.J., Trevisan M., Zeid M., Genco R.J. Identification of periodontal pathogens inatheromatous plaques. J. Periodontol. 2000; 71: 1554–60.
  10. Ford P.J., Gemmell E., Hamlet S.M., Hasan A., Waler P.J., West M.J., Cullinan M.P., Seymour G.J. Cross-reactivityof GroEL antibodies with human heat shock protein60 and quantification of pathogens in atherosclerosis. Oral Microbiol. Immunol. 2005; 20: 296–302.
  11. Inukai J., Inagaki K., Mizuno K., Nakagaki H. Temporalassociation of elevated C-reactive protein and periodontaldisease in men. J. Periodontol. 2009; 80: 734–9.
  12. Weitzberg E., Lundberg J.O. Novel aspects of dietarynitrate and human health. Annu Rev Nutr. 2013; 33: 129–59.
  13. Petersson J., Carlstrom M., Schreiber O., Phillipson M., Christoffersson G., Jagare A., Roos S., Jansson E.A., Persson A.E., Lundberg J.O. et al. Gastroprotective andblood pressure lowering effects of dietary nitrate areabolished by an antiseptic mouthwash. Free Radic. Biol. Med. 2009; 46: 1068–75.
  14. Ivashkin V.T., Drapkina O.M., Buyeverova Ye.L. Potentials of correction of lipid metabolism disorders at patients with metabolic syndrome. Russian Medical News. 2010; 15 (4): 10–20.
  15. Wong J.M., Esfahani A., Singh N., Villa C.R., Mirrahimi A., Jenkins D.J., Kendall C.W. Gut microbiota, diet and heart disease. JAOAC Int. 2012; 95: 24–30.
  16. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbialecology: Human gut microbes associated with obesity. Nature. 2006; 444: 1022–3.
  17. Koeth R.A., Wang Z., Levison B.S., Buffa J.A., Org E. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576–85.
  18. Tang W.H., Wang Z., Levison B.S., Koeth R.A., Britt E.B. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013; 368: 1575–84.
  19. Wang Z., Klipfell E., Bennett B.J., Koeth R., Levison B.S. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472: 57–63.
  20. Ufnal M. Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J. Cardiol. 2014; 30 (12): 1700–5.
  21. Tang H.W., Wang Z., Wu Y., Fan Y., Koeth R.A., Hazen S. Gut Flora Metabolite Trimethylamine N-Oxide Predicts Incident Cardiovascular Risks in Both Stable Non-Diabetics and Diabetic Subjects. JACC. 2013; 61: 10.
  22. Tang W.H., Wang Z., Wu Y., Fan Y., Koeth R.A. Prognostic Value of Elevated Levels of Intestinal Microflora-Generated Metabolite Trimethylamine N-Oxide in Patients with Heart Failure: The Gut Hypothesis Revisited. JACC. 2013; 61: 10.
  23. Koeth R.A., Levison B.S., Culley M.K., Buffa J.A., Wang Z., Gregory J.C., Org E., Wu Y., Li L., Smith J.D., Tang W.H., DiDonato J.A., Lusis A.J., Hazen S. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 2014; 20 (5): 799–812.