350 rub
Journal №8 for 2014 г.
Article in number:
Endothelial dysfunction: associations with functional variants of clinically relevant genes
Keywords: endothelial dysfunction flow-mediated dilatation gene polymorphisms eNOS ACE IL-6
Authors:
A.B. Chukhlovin - Dr.Sc. (Med.), Pavlov First Saint Petersburg State Medical University; Federal Almazov Medical Research Centre
N.D. Elshin - Post-graduate Student, Pavlov First Saint Petersburg State Medical University
N.A. Kuzubova - Post-graduate Student, Pavlov First Saint Petersburg State Medical University
Areg A.Totolian - Dr.Sc. (Med.), Professor, Institute of Epidemiology and Microbiology of the Pasteur; Federal Almazov Medical Research Centre
Abstract:
Endothelial dysfunction is generally defined a systemic imbalance between vasodilatory and vasoconstrictory factors. This disorder may accompany a lot of clinical conditions. The aim of present study was to review some known mechanisms of endothelial regulation, using available publications on functional gene variants that were shown to be associated with standardized parameters of endothelial dysfunction (e.g., FMD test, Celermajer et al., 1992). We have analyzed a number of cross-sectional population studies employing both FMD technique and PCR assays of gene polymorphisms for physiologically relevant enzymes and receptor molecules. Current studies performed in healthy persons of different age, as well as patients with common cardiovascular disorders, diabetes mellitus, etc. have shown that certain functional variants of endothelial nitric oxide synthase (eNOS), ACE, ADRB, as well as IL-6 and some other genes may be involved into pathogenesis of endothelial dysfunction, both in healthy and disease states. Associations between the eNOS polymorphisms and altered FMD tests are mostly documented for atherosclerosis and diabetes mellitus. Appropriate associations between endothelial responses and genetic regulation of renin/angiotensin system, as well as cytokine gene variants deserve further studies in representative clinical samples.
Pages: 13-21
References

  1. Deanfield J., Donald A., Ferri C., Giannattasio C., Halcox J., Halligan S., Lerman A., Mancia G., Oliver J.J., Pessina A.C., Rizzoni D., Rossi G.P., Salvetti A., Schiffrin E.L., Taddei S., Webb D.J. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension // J. Hypertens. 2008. V. 23. P. 7 - 17.
  2. Ludmer P.L., Selwyn A.P., Shook T.L., Wayne R.R., Mudge G.H., Alexander R.W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries // N. Engl. J. Med. 1986. V. 315. P. 1046 - 1051.
  3. Celermajer D.S., Sorensen K.E., Gooch V.M., Spiegelhalter D.J., Miller O.I., Sullivan I.D., Lloyd J.K., Deanfield J.E. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis // Lancet. 1992. V. 340. P. 1111 - 1115.
  4. Celermajer D.S., Sorensen K.E., Bull C., Robinson J., Deanfield J.E. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction // J. Am. Coll. Cardiol. 1994. V. 24. P. 1468 - 1474.
  5. Hamburg N.M., Keyes M.J., Larson M.G., Vasan R.S., Schnabel R., Pryde M.M., Mitchell G.F., Sheffy J., Vita J.A., Benjamin E.J. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study // Circulation. 2008. V. 117. P. 2467 - 2474.
  6. Celermajer D.S. Reliable Endothelial Function Testing: At Our Fingertips - // Circulation. 2008. V. 117. P. 2428 - 2430.
  7. Hirata Y., Nagata D., Suzuki E., Nishimatsu H., Suzuki J., Nagai R. Diagnosis and treatment of endothelial dysfunction in cardiovascular disease // Int. Heart J. 2010. V. 51. № 1. P. 1 - 6.
  8. Jones L.C., Hingorani A.D. Genetic regulation of endothelial function // Heart. 2005. V. 91. P. 1275 - 1277.
  9. Levy A.S., Chung J.C., Kroetsch J.T., Rush J.W. Nitric oxide and coronary vascular endothelium adaptations in hypertension // Vasc. Health Risk Manag. 2009. V. 5. P. 1075 ? 1087.
  10. Channon K. M., Guzik T.J. Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors // J. Physiol. Pharmacol. 2002. V. 53. № 4. P. 515 - 524.
  11. Sayed-Tabatabaei F.A., Oostra B.A., Isaacs A., van Duijn C.M., Witteman J.C. ACE polymorphisms // Circ. Res. 2006. Vol. 98. № 9. P. 1123 - 1133.
  12. Minushkina L.O., Zatejshhikov D.A., Kudryashova O.Ju., Chistyakov D.A., Nosikov V.V., Cimbalova T.E., Barinov V.G., Nosenko E.M., Sedov V.P., Sidorenko B.A. Disfunkcziya e'ndoteliya: svyaz' s polimorfizmom gena reczeptora (tip 1) angiotenzina II u bol'ny'x ishemicheskoj bolezn'yu serdcza // Kardiologiya. 2000. № 1. C. 20 ? 24.
  13. Baranov V.S. (red.) Geneticheskij pasport - osnova individual'noj i prediktivnoj medicziny' // SPb.: N-M. 2009.
  14. Popkova T.V., Novikova D.S., Nasonov E.L. Interlejkin-6 i serdechno-sosudistaya patologiya pri revmatoidnom artrite // Nauchno-prakticheskaya revmatologiya. 2011. № 4. C. 64 - 72.
  15. Konenkov V.I., Shevchenko A.V., Prokof'ev V.F., Maksimov V.N. Kompleks genotipov czitokinov kak geneticheskij faktor riska razvitiya infarkta miokarda u muzhchin evropeoidnogo naseleniya Rossii // Kardiologiya. 2012. T. 52. № 7. C. 22 - 29.
  16. Paradossi U., Manfrini O., Ciofini E., Pizzi C., Biagini A., Xhyheri B., Colombo M.G. Weight is an independent predictor of vascular injury in healthy volunteers with aspartate allele // J. Cardiovasc. Med. (Hagerstown). 2012. V. 13. № 5. P. 307 - 312.
  17. Delgado-Lista J., Garcia-Rios A., Perez-Martinez P., Fuentes F., Jiménez-Gomez Y., Gomez-Luna M.J., Parnell L.D., Marin C., Lai C.Q., Perez-Jimenez F., Ordovas J.M., Lopez-Miranda J. Gene variations of nitric oxide synthase regulate the effects of a saturated fat rich meal on endothelial function // Clin. Nutr. 2011. V. 30. № 2. P. 234 - 238.
  18. Jiménez-Morales A.I., Ruano J., Delgado-Lista J., Fernandez J.M., Camargo A., López-Segura F., Villarraso J.C., Fuentes-Jiménez F., López-Miranda J., Pérez-Jiménez F. NOS3 Glu298Asp polymorphism interacts with virgin olive oil phenols to determine the postprandial endothelial function in patients with the metabolic syndrome // J. Clin. Endocrinol. Metab. 2011. V. 96. № 10 : E1694 - 1702.
  19. Battelino N., Sebestjen M., Keber I., Blagus R., Hovnik T., Bratina N., Battelino T. Endothelial nitric oxide synthase T(?786)C polymorphism in children and adolescents with type 1 diabetes and impaired endothelium-dependent dilatation // Horm. Res. Paediatr. 2011. V. 76. № 4. P. 248 - 253.
  20. Fatini C., Sticchi E., Cesari F., Gori A.M., Cioni G., De Stefano M., Bertoni E., Paudice N., Salvadori M., Zanazzi M., Abbate R. Relationship among endothelial response to hyperemia, bone marrow-derived progenitor cells, and parathyroid hormone in renal transplantation // Transplantation. 2012. V. 93. № 8. P. 835 - 841.
  21. Berezikova E.N., Popova A.A., Teplyakov A.T., Shilov S.N., Mayanskaya S.D., Jakovleva N.F., Luksha E.B., Grebenkina I.A., Zaxarova T.I., Egorova L.S., Kaz'mina V.Ju. Geneticheskie prediktory' razvitiya e'ndotelial'noj disfunkczii u bol'ny'x ishemicheskoj bolezn'yu serdcza, oslozhnennoj xronicheskoj serdechnoj nedostatochnost'yu // Sibirskoe mediczinskoe obozrenie. 2010. № 1. C. 26 - 29.
  22. Fan M., Raitakari O.T., Kähönen M., Juonala M., Hutri-Kähönen N., Marniemi J., Rontu R., Pörsti I., Viikari J., Lehtimäki T. CYBA C242T gene polymorphism and flow-mediated vasodilation in a population of young adults: the Cardiovascular Risk in Young Finns Study // J. Hypertens. 2007. V. 25. № 7. P. 1381 - 1387.
  23. Tounian A., Aggoun Y., Lacorte J.M., Dubern B., Clément K., Bonnet D., Tounian P. Influence of polymorphisms in candidate genes on early vascular alterations in obese children // Arch. Cardiovasc. Dis. 2010. V. 103. № 1. P. 10 - 18.
  24. Méthot J., Hamelin B.A., Arsenault M., Bogaty P., Plante S., Poirier P. The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women // Menopause. 2006. V. 13. № 6. P. 959 - 966.
  25. Kuzubova N.A., Chuxlovin A.B., Morozova E.B., Totolyan A.A. Rol' funkczional'ny'x variantov genov MMP-1, MMP-3, ACE-1 i 5-HTT v formirovanii nekotory'x osobennostej techeniya xronicheskoj obstruktivnoj bolezni legkix // Molekulyarnaya mediczina. 2009. № 2. C. 14 - 19.
  26. Kuzubova N.A., Chukhlovin A.B., Morozova E.B., Totolian A.A., Titova O.N. Common intronic D variant of ACE gene is associated with endothelial dysfunction in COPD // Respiratory Medicine. 2013. V. 107. P. 1217 - 1221.
  27. Mal'czeva L.I., Pavlova T.V. Geneticheskie aspekty' gestoza // Prakticheskaya mediczina. 2011. V. 6. № 11. P. 7 - 12.
  28. Heinonen P., Jartti L., Järvisalo M.J., Pesonen U., Kaprio J.A., Rönnemaa T., Raitakari O.T., Scheinin M. Deletion polymorphism in the alpha2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery // Clin. Sci. 2002. V. 103. № 5. P. 517 - 524.
  29. Cipollone F., Toniato E., Martinotti S., Fazia M., Iezzi A. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke // JAMA. 2004. V. 291. P. 2221 - 2228
  30. Collings A., Raitakari O.T., Juonala M., Rontu R., Kähönen M., Hutri-Kähönen N., Rönnemaa T., Marniemi J., Viikari J.S., Lehtimäki T. Associations of methylenetetrahydrofolate reductase C677T polymorphism with markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study // Scand. J. Clin. Lab. Invest. 2008. V. 68. № 1. P. 22 - 30.
  31. Tischendorf J.J., Yagmur E., Scholten D., Vidacek D., Koch A., Winograd R., Gressner A.M., Trautwein C., Wasmuth H.E., Lammert F. The interleukin-6 (IL6)-174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6 // Int. J. Immunogenet. 2007. V. 34. № 6. P. 413 - 418.
  32. Brull D.J., Leeson C.P., Montgomery H.E., Mullen M., deDivitiis M., Humphries S.E., Deanfield J.E. The effect of the Interleukin-6-174G > C promoter gene polymorphism on endothelial function in healthy volunteers // Eur. J. Clin. Invest. 2002. V. 32. № 3. P. 153 - 157.
  33. Stoica A.L., Stoica E., Constantinescu I., Uscatescu V., Ginghina C. Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysfunction, and postoperative prognosis in patients with peripheral arterial disease // J. Vasc. Surg. 2010. V. 52. № 1. P. 103 - 109.
  34. Charakida M., Donald A.E., Leary S., Halcox J.P., Turner M.W., Johnson M., Loukogeorgakis S.P., Okorie M.I., Davey Smith G., Deanfield J.E., Klein N.J. Endothelial response to childhood infection: the role of mannose-binding lectin (MBL) // Atherosclerosis. 2010. V. 208. № 1. P. 217 - 221.
  35. Jaakkola U., Kakko T., Seppälä H., Vainio-Jylhä E., Vahlberg T., Raitakari O.T., Kallio J. The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is associated with increased levels of inflammatory markers preceding vascular complications in patients with type 2 diabetes // Microvasc. Res. 2010. V. 80. № 3. P. 433 - 439.
  36. Saltiki K., Stamatelopoulos K., Voidonikola P., Lazaros L., Mantzou E., Georgiou I., Anastasiou E., Papamichael C., Alevizaki M. Association of the SHBG gene promoter polymorphism with early markers of atherosclerosis in apparently healthy women // Atherosclerosis. 2011. V. 219. № 1. P. 205 - 210.
  37. Ingelsson E., Syvänen A.C., Lind L. Polymorphisms in the estrogen receptor alpha gene and endothelial function in resistance and conduit arteries in the elderly // Atherosclerosis. 2008. V. 199. № 1. P. 162 - 171.