MODERN MOLECULAR-GENETIC MARKERS IN DIAGNOSTICS AND SCREENING OF EFFICIENCY OF CARDIOVASCULAR DISEASES THERAPY OF CARDIOVASCULAR SYSTEM

Pavlov S. V., Burlaka K. A.

LITERATURE REVIEWS

Scentific article

Cardiovascular diseases occupy one of the most significant health problems. Scientists are actively searching for new methods of diagnosis, validity of hospitalization and quality control of treatment. Biomarkers deserve great attention, some of which, at the moment, are used in everyday clinical practice and reflect the various pathophysiological processes present in cardiovascular diseases. The most well-known of these are: natriuretic peptide, high-sensitivity troponins (hs-cTn), cardiac protein, fatty acid-binding (H-FABP), glutathione transferase P1 (GSTP1), galectin-3, ST2, growth differentiation factor 15 (GDF-15), extracellular heat shock protein 70 (Hsp70), hypoxia induced factor (HIF-1α), Klotho protein, endothelial NO synthase. The clinical value of one marker in both diagnosis and prognosis of outcomes for cardiovascular diseases is limited, since one marker is not prognostically significant. The future use of biomarkers is the use of multimarker panels, which include a specific combination of biomarkers, reflecting the various pathophysiological processes that underlie cardiovascular diseases. For effective use in the diagnosis and treatment of diseases of the cardiovascular system of molecular markers, it is necessary to observe such factors as age, sex, obesity, fraction of the ejection of the left ventricle. The use of biomarkers in practical medicine facilitates rapid more accurate diagnosis of cardiovascular pathologies and screening for the effectiveness of therapy.

biomarkers, cardiovascular diseases, molecular-genetic markers, prognostic value

1. Voronkov LG, Filatova OL, Lyashenko AV, Tkach NA, Lipkan NG. Vizhivanist uprodovzh 24 misyatsiv ta yiyi prediktori v patsientiv iz hronichnoyu sertsevoyu nedostatnistyu i znizhenoyu fraktsieyu vikidu livogo shlunochka zalezhno vid stati. Ukrayinskiy kardiologichniy zhurnal. 2017;6:505. [in Ukrainian].
2. Ipatov AV, Korobkin YuI, Drozdova IV, Hanyukova IYa, Sidorova MG. Hvorobi sistemi krovoobigu: providni tendentsiyi dinamiki invalidnosti. Ukrayinskiy kardiologichniy zhurnal. 2012;1:36-41. [in Ukrainian].
3. Savic-Radojevic A, Pljesa-Ercegovac M, Matic M, Simic D, Radovanovic S, Simic T. Novel Biomarkers of Heart Failure. Advances in Clinical Chemistry. 2017;79:93-152.
4. Maksimov ML, Gyamdzhyan KA, Kukes VG, Goroshko OA. Galektin-3 – novyiy biomarker hronicheskoy serdechnoy nedostatochnosti. Atmosfera. Novosti kardiologii. 2014;3:17-21. [in Russian].
5. Bugrimova MA, Savina NM, Vanieva OS, Sidorenko BA. Mozgovoy natriyureticheskiy peptid kak marker i faktor prognoza pri hronicheskoy serdechnoy nedostatochnosti. Kardiologiya. 2006;1:51-7. [in Russian].
6. Ala-Kopsala M, Magga J, Peuhkurinen Ket, Leipälä J, Ruskoaho H, Leppäluoto J, et al. Molecular heterogeneity has a major impact on the measurement of circulating N-terminal fragments of A- and B-type natriuretic peptides. Clin. Chem. 2004;50:1576-88.
7. Luchner A, Hengstenberg C, Lowel H, Trawinski J, Baumann M, Riegger GA, et al. N-terminal pro-brain natriuretic peptide after myocardial infarction: a marker of cardio-renal function. Hypertension. 2002;39:99-104.
8. Weber M, Hamm C. Role of B-type natriuretic peptide (BNP) and Nt-proBNP in clinical routine. Heart. 2006;92:843-9.
9. Anand I, Fisher L, Chiang Y, Latini R, Masson S, Maggioni AP, et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the valsartan heart fealure trial (Val-HeFT). Circulation. 2003;107:1276-81.
10. Andreev DA, Ryikova MS. Natriyureticheskie peptidyi V-tipa pri serdechnoy nedostatochnosti. Klin. med. 2004;6:4-8. [in Russian].
11. Goluhova EZ, Teryaeva NB, Alieva AM. Natriyureticheskie peptidyi – markeryi i faktoryi prognoza pri hronicheskoy serdechnoy nedostatochnosti. Kreativnaya kardiologiya. 2007;1-2:126-36. [in Russian].
12. Thygesen K, Alpert JS, White HD. Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. 2007;28:2525-38.
13. Chenevier-Gobeaux C, Bonnefoy-Cudraz E, Charpentier S, Dehoux M, Lefevre G, Meune C, et al. Highsensitivity cardiac troponin assays: answers to frequently asked questions. Arch. Cardiovasc. 2015;108:132-49.
14. Kremneva LV, Suplotov SN, Shalaev SV. Otsenka vyisokochuvstvitelnyih testov na troponin v diagnostike ostrogo koronarnogo sindroma. Ration Pharmacother Cardiol. 2016;12(2):204-9. [in Russian].
15. Mills NL, Churchhouse AM, Lee KK, Anand A, Gamble D, Shah AS, et al. Implementation of a sensitive troponin i assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA. 2011;305(12):1210-6.
16. Mills NL, Lee KK, McAllister DA, Churchhouse AM, MacLeod M, Stoddart M, et al. Implications of lowering threshold of plasma troponin concentration in diagnosis of myocardial infarction. BMJ. 2012;344:1533-44.
17. Koroleva LYu, Golitsyina NA, Nosov VP, Zlobin MV, Sobol YuN, Gurvich EV, i dr. Vyisokochuvstvitelnyiy troponin v diagnostike infarkta miokarda: realnaya diagnosticheskaya tsennost ili pereotsenennyie vozmozhnosti. Meditsinskiy almanah. 2017;3:165-8. [in Russian].
18. Pascual-Figal DA, Casas T, Ordonez-Lianes J, Manzano-Fernández S, Bonaque JC, Boronat M, et al. Highly sensitive troponin T for risk stratification of acutely destabilized heart failure. Am Heart Journal. 2012;163(6):1002-10.
19. Colli A, Josa M, Pomar J, Mestres CA, Gherli T. Heart fatty acid binding protein in the diagnosis of myocardial infarction: where do we stand today. Cardiology. 2007;108:4-10.
20. Lescuyer P, Allard L, Hochstrasser D, Sanchez JC. Heart-fatty acid-binding protein as a marker for early detection of acute myocardial infarction and stroke. Mol. Diagn. 2005;9:1-7.
21. Pelsers M, Chapelle J, Glatz J, Vermeer C, Muijtjens AM, Hermens WT, et al. Influence of age and sex and day-to-day and within-day biological variation on plasma concentrations of fatty acid-binding protein and myoglobin in healthy subjects. Clin. Chem. 1999;45(3):441-4.
22. Salnikov AS, Sorokina NN, Rukavishnikov MYu, Ofitserov VI. Belok, svyazyivayuschiy zhirnyie kislotyi, serologicheskiy marker porazheniy miokarda. Sibirskiy nauchnyiy meditsinskiy zhurnal. 2012;32(1):86-92. [in Russian].
23. Lescuyer P, Allard L, Hochstrasser DF, Sanchez JC. Heart-fatty acid-binding protein as a marker for early detection of acute myocardial infarction and stroke. Mol Diagn. 2005;9:1-7.
24. Titov VN. Diagnosticheskoe znachenie soderzhaniya v plazme krovi troponina i belka kardiomiotsitov, svyazyivayuschego zhirnyie kislotyi pri ostrom koronarnom syndrome. Russian Clinical laboratory Diagnostics. 2016;61(10):672-80. [in Russian].
25. Martyinov AI, Voevoda MI, Arutyunov GP, Kokorin VA, Spasskiy AA, Mihaylov AA. Vozmozhnosti ranney diagnostiki ostrogo infarkta miokarda s pomoschyu belka, svyazyivayuschego zhirnyie kislotyi. Rossiyskoe mnogotsentrovoe issledovanie ISPOLIN. Arhiv vnutrenney meditsinyi. 2012;2:40-5. [in Russian].
26. Ishii J, Wang JH, Naruse H, Taga S, Kinoshita M, Kurokawa H, et al. Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid-binding protein in early detection of acute myocardial infarction. Clin. Chem. 1997;43:1372-8.
27. Nakata T, Hashimoto A, Hase M, Tsuchihashi K, Shimamoto K. Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome. Cardiology. 2003;99:96-104.
28. Bhat MA, Gandhi G. Glutathione S-transferase P1 gene polymorphisms and susceptibility to coronary artery disease in a subgroup of north Indian population. Journal of Genetics. 2017;6:927-32.
29. Andrukhova O, Salama M, Rosenhek R, Matthias G, Perkmann T, Steindl J, et al. Serum glutathione S-transferase P1 1 in prediction of cardiac function. J. Card. Fail. 2012;18:253-61.
30. Andrukhova O, Salama M, Krssak M. Single-dose GSTP1 prevents infarction-induced heart failure. J. Card. Fail. 2014;20:135-45.
31. Sharma UC, Pokharel S, Van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121-8.
32. Karlsson A, Christenson K, Matlak M, Björstad A, Brown KL, Telemo E, et al. Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils. Glycobiology. 2009;19:16-20.
33. Tang WH, Shrestha K, Shao Z, Borowski AG, Troughton RW, Thomas JD, et al. Usefulness of plasma galectin-3 levels in systolic heart failure to predict renal insufficiency and survival. Am J Cardiol. 2011;108:385-90.
34. Lopez-Andrès N, Rossignol P, Iraqi W, Fay R, Nuée J, Ghio S, et al. Association of galectin-3 and fibrosis markers with long-term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony: insights from the CARE-HF (Cardiac Resynchronization in Heart Failure) trial. Eur J Heart Fail. 2012;14:74-81.
35. De Boer RA, van Veldhuisen J, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, et al. The fibro sis marker galectin-3 and outcome in general population. J. Intern. Med. 2012;272:55-64.
36. Maksimov ML, Gyamdzhyan KA, Kukes VG, Goroshko OA. Galektin-3 – novyiy biomarker hronicheskoy serdechnoy nedostatochnosti. Atmosfera. Novosti kardiologii. 2014;3:17-21. [in Russian].
37. Melnik AA. ST2 (stimuliruyuschiy faktor rosta) – tsennyiy prognosticheskiy marker pri serdechno-sosudistyih zabolevaniyah. Zdorov’ya Ukrayini 21 storichchya. 2016;20:74-5. [in Russian].
38. Weinber EO. ST2 protein in heart disease: From discovery to mechanisms and prognostic value. Biomaerk Med. 2009;3:495-511.
39. Schmieder A, Multhoff G, Radons J. Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in higly metastatic human pancreatic carcinoma cells. Cytokine. 2012;60:514-21.
40. Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M, et al. A novel cardiac bio-mareker: ST2: a review. Molecules. 2013;18:15314-28.
41. Rehman SU, Mueller Т, James LJ. Characteristics of the Novel Interleukin Family Biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol. 2008;52:1458-65.
42. Januzzi JL, Peacock WF, Maisel AS, Chae CU, Jesse RL, Baggish AL, et al. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study. J Am Coll Cardiol. 2007;50(7):607-13.
43. Chukaeva II, Ahmatova FD, Horeva MV, Kovalchuk LV. Novyie markeryi hronicheskoy serdechnoy nedostatochnosti: aspektyi vospaleniya. Lechebnoe delo. 2016;1:4-7. [in Russian].
44. Rehman SU, Mueller T, Januzzi JL. Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol. 2008;52(18):1458-65.
45. Dieplinger B, Januzzi JL, Steinmair M, Gabriel C, Poelz W, Haltmayer M, et al. Analytical and clinical evaluation of a novel high-sensitivity assay for measurement of soluble ST2 in human plasma – the Presage ST2 assay. Clin Chim Acta. 2009;409(1-2):33-40.
46. Kopitsa NP, Belaya NV, Titarenko NV. Metodyi diagnostiki miokardialnogo fibroza u bolnyih arterialnoy gipertenziey. Arterialnaya gipertenziya. 2008;2:12-5. [in Russian].
47. Santhanakrishnan R, Chong JP, Ng TP, Ling LH, Sim D, Leong KT, et al. Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur. J. Heart Fail. 2012;14(12):1338-47.
48. Argmann CA, Van Den Diepstraten CH, Sawyez CG, Edwards JY, Hegele RA, Wolfe BM, et al. Transforming growth factor-beta 1 inhibits macrophage cholesterol ester accumulation induced by native and oxidized VLDL remnants. Arterioscler Thromb Vasc Biol. 2001;21(12):2011-8.
49. Soboleva AI, Ezhov MV, Polevaya TYu, Matchin YuG. Rol novyih tsitokinov: rostovogo faktoradifferentsirovki 15 (gdf-15) i hryaschevogo glikoproteina 39 (ykl-40) v razvitii i progressirovanii ateroskleroza koronarnyih arteriy. Klinitsist. 2012;3:19-22. [in Russian].
50. Syivolap VD, Zemlyanoy YaV. Vzaimosvyaz rostovogo faktora differentsirovki 15, n-terminalnogo fragmenta mozgovogo natriyureticheskogo peptida s remodelirovaniem serdtsa u bolnyih serdechnoy nedostatochnostyu s sohranennoy fraktsiey vyibrosa posle perenesennogo infarkta miokarda s arterialnoy gipertenziey. Nauchnyie vedomosti Seriya Meditsina. Farmatsiya. 2014;18(189).Vyipusk 27:68-73. [in Russian].
51. Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387-95.
52. Evdonin AL, Medvedeva ND. Vnekletochnyiy belok teplovogo shoka 70 i ego funktsii. Tsitologiya. 2009;51:130-7. [in Russian].
53. Belenichev IF. Rol belkov teplovogo shoka v realizatsii molekulyarno-biohimicheskih mehanizmov neyroprotektsii. FarmakologIya ta likarska toksikologIya. 2013;6(36):72-80. [in Russian].
54. Babushkina IV, Runovich AA, Borovskiy GB. Endogennaya zaschita miokarda: rol belkov teplovogo shoka v mehanizmah prekonditsionirovaniya. Byulleten VSNTs SO RAMN. 2006;5(51):27-31. [in Russian].
55. Shahnovich PG, Margulis BA, Svistov AS. Tsitoprotektivnaya rol endogennyih belkov teplovogo shoka pri lechenii bolnyih s ostryim koronarnyim sindromom. Klinicheskaya meditsina. 2014;7:37-41. [in Russian].
56. Novikov VE, Levchenkova OS. Gipoksiey indutsirovannyiy faktor (hif-1 α) kakmishen farmakologicheskogo vozdeystviya. Obzoryi po klinicheskoy farmakologii i lekarstvennoy terapii. 2013;11(2):8-16. [in Russian].
57. Zagorska A, Dulak J. HIF-1: knowns and unknowns of hypoxia sensing. Acta Biochimica Polonica. 2004;51:563-85.
58. Qingdong K, Costa M. Hypoxia-Inducible Factor-1. Mol. Pharmacol. 2006;70:1469-80.
59. Lee M, Ryu JK, Piao S, Choi MJ, Kim HA, Zhang LW, et al. Efficient gene expression system using the RTP801 promoter in the corpus cavernosum of high-cholesterol diet-induced erectile dysfunction rats for gene therapy. J Sex Med. 2008;5:1355-64.
60. Scherbak NS, Galagudza MM, Shlyahto EV. Rol indutsiruemogo gipoksiey faktora-1 (hif-1) v realizatsii tsitoprotektivnogo effekta ishemicheskogo i farmakologicheskogo postkonditsionirovaniya. Rossiyskiy kardiologicheskiy zhurnal. 2014;11:70-5. [in Russian].
61. Zhao H, Wang Y, Wu Y, Li X, Yang G, Ma X, et al. Hyperlipidemia does not prevent the cardioprotection by postconditioning against myocardial ischemia/reperfusion injury and the involvement of hypoxia inducible factor-1alpha upregulation. Acta Biochim Biophys Sin (Shanghai). 2009;41(9):745-53.
62. Topchiy II. Izmeneniya soderzhaniya morfogeneticheskih belkov FGF23 i Klotho uvelichivaet risk serdechno-sosudistyih sobyitiy. ShidnoEvropeyskiy zhurnal vnutrishnoyi ta simeynoyi meditsini. 2016;2:28-33. [in Russian].
63. Martin A, David V, Quarles LD. Regulation and Function of the FGF23 / Klotho Endocrine Pathways. Physiol Rev. 2012;92:131-55.
64. Mencke R, Harms G, Mirković K, Struik J, Van Ark J, Van Loon E, et al. Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue. Cardiovasc Res. 2015;108:220-31.
65. Topchiy II. Izmeneniya soderzhaniya morfogeneticheskih belkov FGF23 i Klotho uvelichivayut risk serdechno-sosudistyih sobyitiy. ShidnoEvropeyskiy zhurnal vnutrishnoyi ta simeynoyi meditsini. 2016;2:28-33. [in Russian].
66. Zeldich Ella, Ci-Di Chen, Teresa A. Colvin The Neuroprotective Effect of Klotho is Mediated via Regulation of Members of the Redox System. Journal Biological Chemestry. 2014;289(35):24700-15.
67. Stubbs JR, He N, Idiculla A, Gillihan R, Liu S, David V, et al. Longitudinal evaluation of FGF23 changes and mineral metabolism abnormalities in a mouse model of chronic kidney disease. J Bone Miner Res. 2012;27:38-46.
68. Xie J, Yoon J, An SW, Kuro-o M, Huang CL. Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol. 2015;26:1150-60.
69. Pavlov S, Belenchev I, Kolesnik Yu. Disturbance of HSP 70 Chaperone Activity Is a Possible Mechanism of Mitochondrial Dysfunction. Neurochemical Journal. 2011;5:251-6.
70. Maekawa Y, Ohishi M, Ikushima M, Yamamoto K, Yasuda O, Oguro R, et al. Klotho protein diminishes endothelial apoptosis and senescence via a mitogen-activated kinase pathway. Geriatr Gerontol Int. 2011;11:510-6.
71. Bredt DS, Hwang PM, Glatt C, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991;351:714-8.
72. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J. Biol. Chem. 1993;268:17478-88.
73. Parhomenko AN, Lutay YaM, Irkin OI, Kozhuhov SN, Skarzhevskiy AA, Dosenko VE, i dr. Kliniko-prognosticheskoe znachenie polimorfizma gena endotelialnoy no-sintetazyi u bolnyih s ostryimi koronarnyimi sindromami. Meditsina neotlozhnyih sostoyaniy. 2014;3(58):45-54. [in Russian].
74. Kinay S, Lippy P, Ganz P. Endothelial function and coronary artery disease. Curr. Opin. Lipidol. 2001;12:383-9.
75. Hingorani AD, Liang CF, Fatibene J, Monteith S, Parsons A, Haydock S, et al. A common variant of the endothelial nitric oxide synthase (Glu2983Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999;100:1515-20.

«Bulletin of problems biology and medicine» Issue 2 (144), 2018 year, 49-55 pages, index UDK 616.1-07:577.2.088.7

10.29254/2077-4214-2018-2-144-49-55