lvrachЛечащий ВрачLechaschi Vrach1560-51752687-1181lvrach-678Research ArticleСтатьиНовые подходы в диагностике сердечно-сосудистых заболеванийNew approaches in diagnostics of cardiovascular diseasesДылеваЮ. А.DylevaYu. A.dyleva87@yandex.ruГруздеваО. В.GruzdevaO. V.noemail@neicon.ruУчасоваЕ. Г.UchasovaE. G.noemail@neicon.ruКузьминаА. А.KuzminaA. A.noemail@neicon.ruФГБНУ НИИ КПССЗRussian Federation201923062021021616Copyright © Дылева Ю.А., Груздева О.В., Учасова Е.Г., Кузьмина А.А., 20212021Дылева Ю.А., Груздева О.В., Учасова Е.Г., Кузьмина А.А.Dyleva Y.A., Gruzdeva O.V., Uchasova E.G., Kuzmina A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.lvrach.ru/jour/article/view/678

Обзор посвящен описанию ряда современных технологий, так называемых омикс-технологий, в том числе геномики, транскриптомики, протеомики, метаболомики, липидомики и мультимаркерной стратегии, одной из важных целей которых является разработка биомаркеров для диагностики сердечно-сосудистых заболеваний. Отражены достижения данных методов на сегодняшний день и принципы их применения в современной клинической практике для ранней диагностики заболеваний, а также нерешенные вопросы и дальнейшие перспективы.

The review is devoted to the description of a number of modern technologies called omixes, including genomics, transcriptome, proteomics, metabolomics, lipidomics and multimarker strategy, whose most important goals is the development of biomarkers for the diagnostics of cardiovascular diseases. The article reflects the achievements of these methods to date and the principles of their application in modern clinical practice for the early diagnostics of diseases, unresolved issues and future prospects. 

АнгиологияГеномикаКардиологияЛипидомикаМетаболомикаМультимаркерные стратегииПротеомикаСердечно-сосудистые заболеванияСимпозиумТранскриптомикаgenomicstranscriptomicsproteomicsmetabolomicslipidomicscardiovascular diseasesmultimarker strategiesReferenceshttp://www.who.int/mediacentre/factsheets/fs310/en/[accessed23.07.16].http://www.who.int/mediacentre/factsheets/fs310/en/[accessed23.07.16].Balagopal P. B., de Ferranti S. D., Cook S., Daniels S. R., Gidding S. S., Hayman L. L. et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: ascientific statement from the American Heart Association // Circulation. 2011, 123 (23): 2749–2769. DOI: 10.1161/cir.0b013e31821c7c64.Balagopal P. B., de Ferranti S. D., Cook S., Daniels S. R., Gidding S. S., Hayman L. L. et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: ascientific statement from the American Heart Association // Circulation. 2011, 123 (23): 2749–2769. DOI: 10.1161/cir.0b013e31821c7c64.Goff D. C., Lloyd-Jones D. M., Bennett G., Coady S., D’Agostino R. B., Gibbons R. et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines // Circulation. 2014, 129: S49–73. DOI: 10.1161/01.cir.0000437738.63853.7a.Goff D. C., Lloyd-Jones D. M., Bennett G., Coady S., D’Agostino R. B., Gibbons R. et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines // Circulation. 2014, 129: S49–73. DOI: 10.1161/01.cir.0000437738.63853.7a.Blankenberg S., McQueen M. J., Smieja M., Pogue J., Balion C., Lonn E. et al. Comparative impact of multiple biomarkers and N-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study // Circulation. 2006, 114: 201–8. DOI: 10.1161/circulationaha.105.590927.Blankenberg S., McQueen M. J., Smieja M., Pogue J., Balion C., Lonn E. et al. Comparative impact of multiple biomarkers and N-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study // Circulation. 2006, 114: 201–8. DOI: 10.1161/circulationaha.105.590927.Schnabel R. B., Schulz A., Messow C. M., Lubos E., Wild P. S., Zeller T. et al. Multiple marker approach to risk stratification in patients with stable coronary artery disease // Eur Heart J. 2010, 31 (24): 3024–3031. DOI: 10.1093/eurheartj/ehq322.Schnabel R. B., Schulz A., Messow C. M., Lubos E., Wild P. S., Zeller T. et al. Multiple marker approach to risk stratification in patients with stable coronary artery disease // Eur Heart J. 2010, 31 (24): 3024–3031. DOI: 10.1093/eurheartj/ehq322.Tonkin A. M., Blankenberg S., Kirby A., Zeller T., Colquhoun D. M., Funke-Kaiser A. et al. Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: the LIPID biomarker study // Int J Cardiol. 2015, 201: 499–507. DOI: 10.1016/j. ijcard.2015.07.080.Tonkin A. M., Blankenberg S., Kirby A., Zeller T., Colquhoun D. M., Funke-Kaiser A. et al. Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: the LIPID biomarker study // Int J Cardiol. 2015, 201: 499–507. DOI: 10.1016/j. ijcard.2015.07.080.Sarwar N., Butterworth A. S., Freitag D. F., Gregson J., Willeit P., Gorman D. N. et al. IL6R Genetics Consortium Emerging Risk Factors Collaboration: Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies // Lancet. 2012, 379: 1205–1213. DOI: 10.1016/s0140–6736(11)61931–4.Sarwar N., Butterworth A. S., Freitag D. F., Gregson J., Willeit P., Gorman D. N. et al. IL6R Genetics Consortium Emerging Risk Factors Collaboration: Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies // Lancet. 2012, 379: 1205–1213. DOI: 10.1016/s0140–6736(11)61931–4.Valdes A. M., Glass D., Spector T. D. Omics technologies and the study of human ageing // Nat Rev Genet. 2013, 14: 601–607. DOI: 10.1038/nrg3553.Valdes A. M., Glass D., Spector T. D. Omics technologies and the study of human ageing // Nat Rev Genet. 2013, 14: 601–607. DOI: 10.1038/nrg3553.Hoefer I. E., Steffens S., Ala-Korpela M., B?ck M., Badimon L., Bochaton-Piallat M. L. et al. Novel methodologies for biomarker discovery in atherosclerosis // Eur Heart J. 2015, 36: 2635–42. DOI: 10.1093/eurheartj/ehv236.Hoefer I. E., Steffens S., Ala-Korpela M., B?ck M., Badimon L., Bochaton-Piallat M. L. et al. Novel methodologies for biomarker discovery in atherosclerosis // Eur Heart J. 2015, 36: 2635–42. DOI: 10.1093/eurheartj/ehv236.Zeller T., Blankenberg S., Diemert P. Genomewide association studies in cardiovascular disease an update // Clin Chem. 2011, 58 (1): 92–103. DOI: 10.1373/clinchem.2011.170431.Zeller T., Blankenberg S., Diemert P. Genomewide association studies in cardiovascular disease an update // Clin Chem. 2011, 58 (1): 92–103. DOI: 10.1373/clinchem.2011.170431.Kessler T., Vilne B., Schunkert H. The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease // EMBO Mol Med. 2016, 8: 688–701. DOI: 10.15252/emmm.201506174.Kessler T., Vilne B., Schunkert H. The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease // EMBO Mol Med. 2016, 8: 688–701. DOI: 10.15252/emmm.201506174.Chen H. H., Almontashiri N. A., Antoine D., Stewart A. F. Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion? // Curr Cardiol Rep. 2014, 16 (7): 502. DOI: 10.1007/s11886–014–0502–7.Chen H. H., Almontashiri N. A., Antoine D., Stewart A. F. Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion? // Curr Cardiol Rep. 2014, 16 (7): 502. DOI: 10.1007/s11886–014–0502–7.Boon R. A., Jae N., Holdt L., Dimmeler S. Long noncoding RNAs: from clinical genetics to therapeutic targets? // J Am Coll Cardiol. 2016, 67: 1214–26. DOI: 10.1016/j. jacc.2015.12.051.Boon R. A., Jae N., Holdt L., Dimmeler S. Long noncoding RNAs: from clinical genetics to therapeutic targets? // J Am Coll Cardiol. 2016, 67: 1214–26. DOI: 10.1016/j. jacc.2015.12.051.Smith J. A., Ware E. B., Middha P., Beacher L., Kardia S. L. Current applications of genetic risk scores to cardiovascular outcomes and subclinical phenotypes // Curr Epidemiol Rep. 2015, 2: 180–190. DOI: 10.1007/s40471–015–0046–4.Smith J. A., Ware E. B., Middha P., Beacher L., Kardia S. L. Current applications of genetic risk scores to cardiovascular outcomes and subclinical phenotypes // Curr Epidemiol Rep. 2015, 2: 180–190. DOI: 10.1007/s40471–015–0046–4.Tikkanen E., Havulinna A. S., Palotie A., Salomaa V., Ripatti S. Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease // Arterioscler Thromb Vasc Biol. 2013, 33: 2261–2266. DOI: 10.1161/atvbaha.112.301120.Tikkanen E., Havulinna A. S., Palotie A., Salomaa V., Ripatti S. Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease // Arterioscler Thromb Vasc Biol. 2013, 33: 2261–2266. DOI: 10.1161/atvbaha.112.301120.Ganna A., Magnusson P. K., Pedersen N. L., de Faire U., Reilly M., Arnl?v J. et al. Multilocus genetic risk scores for coronary heart disease prediction // Arterioscler Thromb Vasc Biol. 2013, 33: 2267–2272. DOI: 10.1161/atvbaha.113.301218.Ganna A., Magnusson P. K., Pedersen N. L., de Faire U., Reilly M., Arnl?v J. et al. Multilocus genetic risk scores for coronary heart disease prediction // Arterioscler Thromb Vasc Biol. 2013, 33: 2267–2272. DOI: 10.1161/atvbaha.113.301218.Weijmans M., de Bakker P. I., van der Graaf Y. 3., Asselbergs F. W., Algra A., Jan de Borst G. et al. Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease // Atherosclerosis. 2015, 239: 451–458. DOI: 10.1016/j. atherosclerosis.2015.02.008.Weijmans M., de Bakker P. I., van der Graaf Y. 3., Asselbergs F. W., Algra A., Jan de Borst G. et al. Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease // Atherosclerosis. 2015, 239: 451–458. DOI: 10.1016/j. atherosclerosis.2015.02.008.Siemelink M. A., Zeller T. Biomarkers of coronary artery disease: the promise of the transcriptome // Curr Cardiol Rep. 2014, 16 (8): 513. DOI: 10.1007/s11886–014–0513–4.Siemelink M. A., Zeller T. Biomarkers of coronary artery disease: the promise of the transcriptome // Curr Cardiol Rep. 2014, 16 (8): 513. DOI: 10.1007/s11886–014–0513–4.Sinning C., Zengin E., Zeller T., Schnabel R. B., Blankenberg S., Westermann D. Candidate biomarkers in heart failure with reduced and preserved ejection fraction // Biomarkers. 2015, 20: 258–65. DOI: 10.3109/1354750x.2015.1068856.Sinning C., Zengin E., Zeller T., Schnabel R. B., Blankenberg S., Westermann D. Candidate biomarkers in heart failure with reduced and preserved ejection fraction // Biomarkers. 2015, 20: 258–65. DOI: 10.3109/1354750x.2015.1068856.Jackson C. E., Haig C., Welsh P., Dalzell J. R., Tsorlalis I. K., McConnachie A. The incremental prognostic and clinical value of multiple novel biomarkers in heart failure // Eur J Heart Fail. 2016, 18 (12): 1491–1498. DOI: 10.1002/ejhf.543.Jackson C. E., Haig C., Welsh P., Dalzell J. R., Tsorlalis I. K., McConnachie A. The incremental prognostic and clinical value of multiple novel biomarkers in heart failure // Eur J Heart Fail. 2016, 18 (12): 1491–1498. DOI: 10.1002/ejhf.543.Копьева К. В., Гракова Е. В., Тепляков А. Т. Новые маркеры сердечной недостаточности: значение для диагностики и прогнозирования Nt-proBNP и интерлейкиновых рецепторов — членов семейства ST2 // Комплексные проблемы сердечно-сосудистых заболеваний. 2018, 7 (1): 94–101. DOI: 10.17802/2306-1278-2018-7-1-94-101.Копьева К. В., Гракова Е. В., Тепляков А. Т. Новые маркеры сердечной недостаточности: значение для диагностики и прогнозирования Nt-proBNP и интерлейкиновых рецепторов — членов семейства ST2 // Комплексные проблемы сердечно-сосудистых заболеваний. 2018, 7 (1): 94–101. DOI: 10.17802/2306-1278-2018-7-1-94-101.Дылева Ю. А., Груздева О. В., Учасова Е. Г., Кузьмина А. А., Каретникова В. Н. Стимулирующий фактор роста ST2 в кардиологии: настоящее и перспективы // Лечащий Врач. 2017, 11: 14–38.Дылева Ю. А., Груздева О. В., Учасова Е. Г., Кузьмина А. А., Каретникова В. Н. Стимулирующий фактор роста ST2 в кардиологии: настоящее и перспективы // Лечащий Врач. 2017, 11: 14–38.Coglianese E. E., Larson M. G., Vasan R. S., Ho J. E., Ghorbani A., McCabe E. L. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study // Clin Chem. 2012, 58: 1673–1681. DOI: 10.1373/clinchem.2012.192153.Coglianese E. E., Larson M. G., Vasan R. S., Ho J. E., Ghorbani A., McCabe E. L. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study // Clin Chem. 2012, 58: 1673–1681. DOI: 10.1373/clinchem.2012.192153.Ho J. E., Larson M. G., Ghorbani A., Cheng S., Vasan R. S., Wang T. J. et al. Soluble ST2 predicts elevated SBP in the community // J Hypertens. 2013, 31: 1431–1436. DOI: 10.1097/hjh.0b013e3283611bdf.Ho J. E., Larson M. G., Ghorbani A., Cheng S., Vasan R. S., Wang T. J. et al. Soluble ST2 predicts elevated SBP in the community // J Hypertens. 2013, 31: 1431–1436. DOI: 10.1097/hjh.0b013e3283611bdf.Wang T. J., Wollert K. C., Larson M. G., Coglianese E., McCabe E. L., Cheng S. et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study // Circulation. 2012, 126: 1596–604. DOI: 10.1161/circulationaha.112.129437.Wang T. J., Wollert K. C., Larson M. G., Coglianese E., McCabe E. L., Cheng S. et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study // Circulation. 2012, 126: 1596–604. DOI: 10.1161/circulationaha.112.129437.Sinnaeve P. R., Donahue M. P., Grass P., Seo D., Vonderscher J., Chibout S. D. et al. Gene expression patterns in peripher. al blood correlate with the extent of coronary artery disease // PloS One. 2009, 4: e7037. DOI: 10.1371/journal. pone.0007037.Sinnaeve P. R., Donahue M. P., Grass P., Seo D., Vonderscher J., Chibout S. D. et al. Gene expression patterns in peripher. al blood correlate with the extent of coronary artery disease // PloS One. 2009, 4: e7037. DOI: 10.1371/journal. pone.0007037.Joehanes R., Ying S., Huan T., Johnson A. D., Raghavachari N., Wang R. et al. Gene expression signatures of coronary heart disease // Arterioscler Thromb Vasc Biol. 2013, 33: 1418–1426. DOI: 10.1161/atvbaha.112.301169.Joehanes R., Ying S., Huan T., Johnson A. D., Raghavachari N., Wang R. et al. Gene expression signatures of coronary heart disease // Arterioscler Thromb Vasc Biol. 2013, 33: 1418–1426. DOI: 10.1161/atvbaha.112.301169.Thomas G. S., Voros S., McPherson J. A., Lansky A. J., Winn M. E., Bateman T. M. et al. A blood-based gene expression test for obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for yocardial perfusion imaging the COMPASS study // Circ Cardiovasc Genet. 2013, 6: 154–162. DOI: 10.1161/circgenetics.112.964015.Thomas G. S., Voros S., McPherson J. A., Lansky A. J., Winn M. E., Bateman T. M. et al. A blood-based gene expression test for obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for yocardial perfusion imaging the COMPASS study // Circ Cardiovasc Genet. 2013, 6: 154–162. DOI: 10.1161/circgenetics.112.964015.Kaudewitz D., Zampetaki A., Mayr M. MicroRNA biomarkers for coronary artery disease? Curr Atheroscler Rep. 2015, 17 (12): 70. DOI: 10.1007/s11883-015-0548-z.Kaudewitz D., Zampetaki A., Mayr M. MicroRNA biomarkers for coronary artery disease? Curr Atheroscler Rep. 2015, 17 (12): 70. DOI: 10.1007/s11883-015-0548-z.Memczak S., Papavasileiou P., Peters O., Rajewsky N. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood // PloS One. 2015, 10: e0141214. DOI: 10.1371/journal. pone.0141214.Memczak S., Papavasileiou P., Peters O., Rajewsky N. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood // PloS One. 2015, 10: e0141214. DOI: 10.1371/journal. pone.0141214.Van Rooij E. The art of microRNA research // Circ Res. 2011, 108: 219–234. DOI: 10.1161/circresaha.110.227496.Van Rooij E. The art of microRNA research // Circ Res. 2011, 108: 219–234. DOI: 10.1161/circresaha.110.227496.Mitchell P. S., Parkin R. K., Kroh E. M., Fritz B. R., Wyman S. K., Pogosova-Agadjanyan E. L. et al. Circulating microRNAs as stable blood-based markers for cancer detection // Proc Natl Acad Sci USA. 2008, 105: 10513–10518. DOI: 10.1073/pnas.0804549105.Mitchell P. S., Parkin R. K., Kroh E. M., Fritz B. R., Wyman S. K., Pogosova-Agadjanyan E. L. et al. Circulating microRNAs as stable blood-based markers for cancer detection // Proc Natl Acad Sci USA. 2008, 105: 10513–10518. DOI: 10.1073/pnas.0804549105.Schulte C., Zeller T. MicroRNA-based diagnostics and therapy in cardiovascular disease-summing up the facts // Cardiovasc Diagn Ther. 2015, 5: 17–36. DOI: 10.3978/j. issn.2223–3652.2014.12.03.Schulte C., Zeller T. MicroRNA-based diagnostics and therapy in cardiovascular disease-summing up the facts // Cardiovasc Diagn Ther. 2015, 5: 17–36. DOI: 10.3978/j. issn.2223–3652.2014.12.03.Busch A., Eken S. M., Maegdefessel L. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease // Ann Transl Med. 2016, 4: 236. DOI: 10.21037/atm.2016.06.06.Busch A., Eken S. M., Maegdefessel L. Prospective and therapeutic screening value of non-coding RNA as biomarkers in cardiovascular disease // Ann Transl Med. 2016, 4: 236. DOI: 10.21037/atm.2016.06.06.Karakas M., Schulte C., Appelbaum S., Ojeda F., Lackner K. J., M?nzel T. et al. Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease — results from the large AtheroGene study // Eur Heart J. 2017, 14: 38 (7): 516–523. DOI: 10.1093/eurheartj/ehw250.Karakas M., Schulte C., Appelbaum S., Ojeda F., Lackner K. J., M?nzel T. et al. Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease — results from the large AtheroGene study // Eur Heart J. 2017, 14: 38 (7): 516–523. DOI: 10.1093/eurheartj/ehw250.Ellis K. L., Cameron V. A., Troughton R. W., Frampton C. M., Ellmers L. J., Richards A. M. Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients // Eur J Heart Fail. 2013, 15: 1138–1147. DOI: 10.1093/eurjhf/hft078.Ellis K. L., Cameron V. A., Troughton R. W., Frampton C. M., Ellmers L. J., Richards A. M. Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients // Eur J Heart Fail. 2013, 15: 1138–1147. DOI: 10.1093/eurjhf/hft078.Luo P., He T., Jiang R., Li G. MicroRNA-423-5p targets O-GlcNAc transferase to induce apoptosis in cardiomyocytes // Mol Med Rep. 2015, 12: 1163–1168. DOI: 10.3892mmr.2015.3491.Luo P., He T., Jiang R., Li G. MicroRNA-423-5p targets O-GlcNAc transferase to induce apoptosis in cardiomyocytes // Mol Med Rep. 2015, 12: 1163–1168. DOI: 10.3892mmr.2015.3491.Luo P., Zhang W. MicroRNA4235p mediates H2O2-induced apoptosis in cardiomyocytes through OGlcNAc transferase // Mol Med Rep. 2016, 14: 857–864. DOI: 10.3892/mmr.2016.5344.Luo P., Zhang W. MicroRNA4235p mediates H2O2-induced apoptosis in cardiomyocytes through OGlcNAc transferase // Mol Med Rep. 2016, 14: 857–864. DOI: 10.3892/mmr.2016.5344.Zampetaki A., Willeit P., Tilling L., Drozdov I., Prokopi M., Renard J. M. et al. Prospective study on circulating microRNAs and risk of myocardial infarction // J Am Coll Cardiol. 2012, 60 (4): 290–299. DOI: 10.1016/j. jacc.2012.03.056.Zampetaki A., Willeit P., Tilling L., Drozdov I., Prokopi M., Renard J. M. et al. Prospective study on circulating microRNAs and risk of myocardial infarction // J Am Coll Cardiol. 2012, 60 (4): 290–299. DOI: 10.1016/j. jacc.2012.03.056.Schulte C., Molz S., Appelbaum S., Karakas M., Ojeda F., Lau D. M. et al. miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease // PloS One. 2015, 10 (12): e0145930. DOI: 10.1371/journal. pone.0145930.Schulte C., Molz S., Appelbaum S., Karakas M., Ojeda F., Lau D. M. et al. miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease // PloS One. 2015, 10 (12): e0145930. DOI: 10.1371/journal. pone.0145930.Pennisi E. Genomics. ENCODE project writes eulogy for junk DNA // Science. 2012, 337: 1159–1161. DOI: 10.1126/science.337.6099.1159.Pennisi E. Genomics. ENCODE project writes eulogy for junk DNA // Science. 2012, 337: 1159–1161. DOI: 10.1126/science.337.6099.1159.Archer K., Broskova Z., Bayoumi A. S., Teoh J. P., Davila A., Tang Y. et al. Long non-coding RNAs as master regulators in cardiovascular diseases // Int J Mol Sci. 2015, 16: 23651–23667. DOI: 10.3390/ijms161023651.Archer K., Broskova Z., Bayoumi A. S., Teoh J. P., Davila A., Tang Y. et al. Long non-coding RNAs as master regulators in cardiovascular diseases // Int J Mol Sci. 2015, 16: 23651–23667. DOI: 10.3390/ijms161023651.Yang Y., Cai Y., Wu G., Chen X., Liu Y., Wang X. et al. Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease // Clin Sci (Lond). 2015, 129 (8): 675–685. DOI: 10.1042/cs20150121.Yang Y., Cai Y., Wu G., Chen X., Liu Y., Wang X. et al. Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease // Clin Sci (Lond). 2015, 129 (8): 675–685. DOI: 10.1042/cs20150121.Cai Y., Yang Y., Chen X., He D., Zhang X., Wen X. et al. Circulating «LncPPARdelta» from monocytes as a novel biomarker for coronary artery diseases // Medicine (Baltimore). 2016, 95 (6): e2360. DOI: 10.1097/md.0000000000002360.Cai Y., Yang Y., Chen X., He D., Zhang X., Wen X. et al. Circulating «LncPPARdelta» from monocytes as a novel biomarker for coronary artery diseases // Medicine (Baltimore). 2016, 95 (6): e2360. DOI: 10.1097/md.0000000000002360.Skroblin P., Mayr M. «Going long»: long non-coding RNAs as biomarkers // Circ Res. 2014, 115 (7): 607–609. DOI: 10.1161/circresaha.114.304839.Skroblin P., Mayr M. «Going long»: long non-coding RNAs as biomarkers // Circ Res. 2014, 115 (7): 607–609. DOI: 10.1161/circresaha.114.304839.Werfel S., Nothjunge S., Schwarzmayr T., Strom T. M., Meitinger T., Engelhardt S. Characterization of circular RNAs in human, mouse and rat hearts // J Mol Cell Cardiol. 2016, 98: 103–107. DOI: 10.1016/j. yjmcc.2016.07.007.Werfel S., Nothjunge S., Schwarzmayr T., Strom T. M., Meitinger T., Engelhardt S. Characterization of circular RNAs in human, mouse and rat hearts // J Mol Cell Cardiol. 2016, 98: 103–107. DOI: 10.1016/j. yjmcc.2016.07.007.H?ntzsch M., Tolios A., Beutner F., Nagel D., Thiery J., Teupser D. et al. Comparison of whole blood RNA preservation tubes and novel generation RNA extraction kits for analysis of mRNA and MiRNA profiles // PloS One. 2014, 9: e113298. DOI: 10.1371/journal. pone.0113298.H?ntzsch M., Tolios A., Beutner F., Nagel D., Thiery J., Teupser D. et al. Comparison of whole blood RNA preservation tubes and novel generation RNA extraction kits for analysis of mRNA and MiRNA profiles // PloS One. 2014, 9: e113298. DOI: 10.1371/journal. pone.0113298.Schwarzenbach H., da Silva A. M., Calin G., Pantel K. Data normalization strategies for microRNA quantification // Clin Chem. 2015, 61: 1333–1342. DOI: 10.1373/clinchem.2015.239459.Schwarzenbach H., da Silva A. M., Calin G., Pantel K. Data normalization strategies for microRNA quantification // Clin Chem. 2015, 61: 1333–1342. DOI: 10.1373/clinchem.2015.239459.Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K. et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases // Cell Res. 2008, 18 (10): 997–1006. DOI: 10.1038/cr.2008.282.Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K. et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases // Cell Res. 2008, 18 (10): 997–1006. DOI: 10.1038/cr.2008.282.Atzler D., Schwedhelm E., Zeller T. Integrated genomics and metabolomics in nephrology // Nephrol Dial Transplant. 2014, 29: 1467–1474. DOI: 10.1093/ndt/gft492.Atzler D., Schwedhelm E., Zeller T. Integrated genomics and metabolomics in nephrology // Nephrol Dial Transplant. 2014, 29: 1467–1474. DOI: 10.1093/ndt/gft492.Marcinkiewicz-Siemion M., Ciborowski M., Kretowski A., Musial W. J., Kaminski K. A. Metabolomics — A wide-open door to personalized treatment in chronic heart failure? // Int J Cardiol. 2016, 219: 156–163. DOI: 10.1016/j. ijcard.2016.06.022.Marcinkiewicz-Siemion M., Ciborowski M., Kretowski A., Musial W. J., Kaminski K. A. Metabolomics — A wide-open door to personalized treatment in chronic heart failure? // Int J Cardiol. 2016, 219: 156–163. DOI: 10.1016/j. ijcard.2016.06.022.Roberts L. D., Gerszten R. E. Toward new biomarkers of cardiometabolic diseases // Cell Metab. 2013, 18: 43–50. DOI: 10.1016/j. cmet.2013.05.009.Roberts L. D., Gerszten R. E. Toward new biomarkers of cardiometabolic diseases // Cell Metab. 2013, 18: 43–50. DOI: 10.1016/j. cmet.2013.05.009.Wang Z., Klipfell E., Bennett B. J., Koeth R., Levison B. S., Dugar B. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease // Nature. 2011. 472: 57–63. DOI: 10.1038/nature09922.Wang Z., Klipfell E., Bennett B. J., Koeth R., Levison B. S., Dugar B. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease // Nature. 2011. 472: 57–63. DOI: 10.1038/nature09922.Hartiala J. A., Tang W. H., Wang Z., Crow A. L., Stewart A. F., Roberts R. et al. Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease // Nat Commun. 2016, 7: 10558. DOI: 10.1038/ncomms10558.Hartiala J. A., Tang W. H., Wang Z., Crow A. L., Stewart A. F., Roberts R. et al. Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease // Nat Commun. 2016, 7: 10558. DOI: 10.1038/ncomms10558.Shah S. H., Bain J. R., Muehlbauer M. J., Stevens R. D., Crosslin D. R., Haynes C. et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events // CircCardiovasc Genet. 2010, 3 (2): 207–214. DOI: 10.1161/circgenetics.109.852814.Shah S. H., Bain J. R., Muehlbauer M. J., Stevens R. D., Crosslin D. R., Haynes C. et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events // CircCardiovasc Genet. 2010, 3 (2): 207–214. DOI: 10.1161/circgenetics.109.852814.Rossing K., Bosselmann H. S., Gustafsson F., Zhang Z. Y., Gu Y. M., Kuznetsova T. et al. Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction // PloS One. 2016, 11 (6): e0157167. DOI: 10.1371/journal. pone.0157167.Rossing K., Bosselmann H. S., Gustafsson F., Zhang Z. Y., Gu Y. M., Kuznetsova T. et al. Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction // PloS One. 2016, 11 (6): e0157167. DOI: 10.1371/journal. pone.0157167.Quehenberger O., Dennis E. A. The human plasma lipidome // N Engl J Med. 2011, 365: 1812–1823. DOI: 10.1056/nejmra1104901.Quehenberger O., Dennis E. A. The human plasma lipidome // N Engl J Med. 2011, 365: 1812–1823. DOI: 10.1056/nejmra1104901.Tarasov K., Ekroos K., Suoniemi M., Kauhanen D., Sylv?nne T., Hurme R. et al. Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency // J Clin Endocrinol Metab. 2014, 99: E45–52. DOI: 10.1210/jc.2013–2559.Tarasov K., Ekroos K., Suoniemi M., Kauhanen D., Sylv?nne T., Hurme R. et al. Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency // J Clin Endocrinol Metab. 2014, 99: E45–52. DOI: 10.1210/jc.2013–2559.Morrow D. A., de Lemos J. A. Benchmarks for the assessment of novel cardiovascular biomarkers // Circulation. 2007, 115 (8): 949–952. DOI: 10.1161/circulationaha.106.683110.Morrow D. A., de Lemos J. A. Benchmarks for the assessment of novel cardiovascular biomarkers // Circulation. 2007, 115 (8): 949–952. DOI: 10.1161/circulationaha.106.683110.

The authors declare that there are no conflicts of interest present.