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Новые биомаркеры легочной гипертензии

https://doi.org/10.18087/cardio.2019.7.10259

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Аннотация

Легочная гипертензия (ЛГ) представляет собой клинический синдром, характеризующийся прогрессирующим повышением легочного сосудистого сопротивления, которое приводит к ремоделированию правого желудочка, его недостаточности и преждевременной смерти пациентов. Ранняя диагностика и мониторинг прогрессирования заболевания имеют решающее значение для принятия решений о необходимой терапии. «Золотым стандартом» диагностики ЛГ является катетеризация правых отделов сердца. Для мониторирования течения болезни используется оценка систолического давления в легочной артерии с помощью трансторакальной эхокардиографии. В дополнение к этому существует потребность в неинвазивных биомаркерах, отражающих патологические изменения в сосудах легочной артерии и позволяющих диагностировать ЛГ. В обзоре излагаются данные о таких биомаркерах, как срединный фрагмент проадреномедулина, карбоксиконцевой проэндотелин-1, копептин, асимметричный диметиларгинин, 15-й фактор роста и дифференциации роста, которые классифицируются на основе их зависимости от дисфункции эндотелиальных клеток, воспаления, эпигенетики, функции сердца, окислительного стресса, внеклеточного матрикса. Определение биомаркеров, имеющих диагностическую ценность для прогнозирования тяжести, прогрессирования ЛГ и ответа на терапию, в простом анализе крови или конденсате выдыхаемого воздуха, значительно может снизить затраты на лечение и улучшить ведение больных ЛГ.

Об авторах

В. В. Гайнитдинова
ФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России (Сеченовский Университет)
Россия
Москва


С. Н. Авдеев
ФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России (Сеченовский Университет); ФГБУ «НИИ пульмонологии» ФМБА России
Россия
Москва


Список литературы

1. Чазова И. Е., Авдеев С. Н., Царева Н. А., Волков А. В., Мартынюк Т. В., Наконечников С. Н. Клинические рекомендации по диагностике и лечению легочной гипертонии. Терапевтический архив. 2014;86(9):4-23

2. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). European Heart Journal. 2016;37(1):67–119. DOI: 10.1093/eurheartj/ehv317

3. Nagaya N, Nishikimi T, Uematsu M, Satoh T, Kyotani S, Sakamaki F et al. Plasma Brain Natriuretic Peptide as a Prognostic Indicator in Patients With Primary Pulmonary Hypertension. Circulation. 2000;102(8):865–70. DOI: 10.1161/01.CIR.102.8.865

4. Williams MH, Handler CE, Akram R, Smith CJ, Das C, Smee J et al. Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. European Heart Journal. 2006;27(12):1485–94. DOI: 10.1093/eurheartj/ehi891

5. Takatsuki S, Wagner BD, Ivy DD. B-type Natriuretic Peptide and Amino-terminal Pro-B-type Natriuretic Peptide in Pediatric Patients with Pulmonary Arterial Hypertension: Comparison of Brain Natriuretic Peptides. Congenital Heart Disease. 2012;7(3):259–67. DOI: 10.1111/j.1747-0803.2011.00620.x

6. Неклюдова Г. В., Авдеев С. Н., Баймаканова Г. Е. Хроническая обструктивная болезнь легких и легочная гипертензия: мозговой натрийуретический пептид как маркер легочной гипертензии. Пульмонология. 2013;3:31-5

7. Andreassen AK, Wergeland R, Simonsen S, Geiran O, Guevara C, Ueland T. N-Terminal Pro-B-Type Natriuretic Peptide as an Indicator of Disease Severity in a Heterogeneous Group of Patients With Chronic Precapillary Pulmonary Hypertension. The American Journal of Cardiology. 2006;98(4):525–9. DOI: 10.1016/j.amjcard.2006.02.061

8. Mauritz G-J, Rizopoulos D, Groepenhoff H, Tiede H, Felix J, Eilers P et al. Usefulness of Serial N-Terminal Pro-B-Type Natriuretic Peptide Measurements for Determining Prognosis in Patients With Pulmonary Arterial Hypertension. The American Journal of Cardiology. 2011;108(11):1645–50. DOI: 10.1016/j.amjcard.2011.07.025

9. Al-Naamani N, Palevsky HI, Lederer DJ, Horn EM, Mathai SC, Roberts KE et al. Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension. Annals of the American Thoracic Society. 2016;13(1):25–30. DOI: 10.1513/AnnalsATS.201508-543OC

10. Zelniker T, Uhlmann L, Spaich S, Friedrich J, Preusch MR, Meyer FJ et al. Novel biomarkers for risk stratification in pulmonary arterial hypertension. ERJ Open Research. 2015;1(2):00008–2015. DOI: 10.1183/23120541.00008-2015

11. Sellitti DF, Koles N, Mendonça MC. Regulation of C-type natriuretic peptide expression. Peptides. 2011;32(9):1964–71. DOI: 10.1016/j.peptides.2011.07.013

12. Suga S. Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells. Endocrinology. 1993;133(6):3038–41. DOI: 10.1210/en.133.6.3038

13. Cargill RI, Barr CS, Coutie WJ, Struthers AD, Lipworth BJ. C-type natriuretic peptide levels in cor pulmonale and in congestive heart failure. Thorax. 1994;49(12):1247–9. PMID: 7878562

14. Kaiser R, Grotemeyer K, Lepper P, Stokes C, Bals R, Wilkens H. Associations of circulating natriuretic peptides with haemodynamics in precapillary pulmonary hypertension. Respiratory Medicine. 2015;109(9):1213–23. DOI: 10.1016/j.rmed.2015.02.014

15. Гайнитдинова В. В., Авдеев С. Н., Шарафутдинова Л. А., Губайдуллина Р. Я. Диагностическая и прогностическая значимость N-концевого предшественника натрийуретического пептида С-типа у больных ХОБЛ с легочной гипертензии. Пульмонология. 2015;25(6):693-7

16. Felker GM, Allen LA, Pocock SJ, Shaw LK, McMurray JJV, Pfeffer MA et al. Red Cell Distribution Width as a Novel Prognostic Marker in Heart Failure. Journal of the American College of Cardiology. 2007;50(1):40–7. DOI: 10.1016/j.jacc.2007.02.067

17. Tonelli M, Sacks F, Arnold M, Moye L, Davis B, Pfeffer M. Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease. Circulation. 2008;117(2):163–8. DOI: 10.1161/CIRCULATIONAHA.107.727545

18. Wen Y. High red blood cell distribution width is closely associated with risk of carotid artery atherosclerosis in patients with hypertension. Experimental and Clinical Cardiology. 2010;15(3):37–40. PMID: 20959889

19. Rhodes CJ, Wharton J, Howard LS, Gibbs JSR, Wilkins MR. Red cell distribution width outperforms other potential circulating biomarkers in predicting survival in idiopathic pulmonary arterial hypertension. Heart. 2011;97(13):1054–60. DOI: 10.1136/hrt.2011.224857

20. Fenster BE, Lasalvia L, Schroeder JD, Smyser J, Silveira LJ, Buckner JK et al. Cystatin C: A potential biomarker for pulmonary arterial hypertension: Cystatin C for pulmonary hypertension. Respirology. 2014;19(4):583–9. DOI: 10.1111/resp.12259

21. Sanli C, Oguz D, Olgunturk R, Tunaoglu FS, Kula S, Pasaoglu H et al. Elevated Homocysteine and Asymmetric Dimethyl Arginine Levels in Pulmonary Hypertension Associated With Congenital Heart Disease. Pediatric Cardiology. 2012;33(8):1323–31. DOI: 10.1007/s00246-012-0321-9

22. Ozerol IH, Pac FA, Ozerol E, Ege E, Yologlu S, Temel I et al. Plasma endothelin-1, homocysteine and serum nitric oxide values in patients with left-to-right shunt. Indian Heart Journal. 2004;56(6):653–7. PMID: 15751522

23. Vélez-Martínez M, Ayers C, Mishkin JD, Bartolome SB, García CK, Torres F et al. Association of Cardiac Troponin I With Disease Severity and Outcomes in Patients With Pulmonary Hypertension. The American Journal of Cardiology. 2013;111(12):1812–7. DOI: 10.1016/j.amjcard.2013.02.036

24. Völkers M, Rohde D, Zelniker T, Weiss CS, Giannitsis E, Katus HA et al. High-sensitive Troponin T increase after exercise in patients with pulmonary arterial hypertension. BMC Pulmonary Medicine. 2013;13(1):28. DOI: 10.1186/1471-2466-13-28

25. Khan SQ, O’Brien RJ, Struck J, Quinn P, Morgenthaler N, Squire I et al. Prognostic Value of Midregional Pro-Adrenomedullin in Patients With Acute Myocardial Infarction. Journal of the American College of Cardiology. 2007;49(14):1525–32. DOI: 10.1016/j.jacc.2006.12.038

26. Krüger S, Ewig S, Giersdorf S, Hartmann O, Suttorp N, Welte T. Cardiovascular and Inflammatory Biomarkers to Predict Short- and Long-Term Survival in Community-acquired Pneumonia: Results from the German Competence Network, CAPNETZ. American Journal of Respiratory and Critical Care Medicine. 2010;182(11):1426–34. DOI: 10.1164/rccm.201003-0415OC

27. Silva Marques J, Martins SR, Calisto C, Gonçalves S, Almeida AG, de Sousa JC et al. An exploratory panel of biomarkers for risk prediction in pulmonary hypertension: Emerging role of CT-proET-1. The Journal of Heart and Lung Transplantation. 2013;32(12):1214–21. DOI: 10.1016/j.healun.2013.06.020

28. Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P et al. Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea. Journal of the American College of Cardiology. 2010;55(19):2062–76. DOI: 10.1016/j.jacc.2010.02.025

29. Kolditz M, Seyfarth H-J, Wilkens H, Ewert R, Bollmann T, Dinter C et al. MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH. Lung. 2015;193(6):901–10. DOI: 10.1007/s00408-015-9802-y

30. Heresi GA, Aytekin M, Newman J, DiDonato J, Dweik RA. Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine. 2010;182(5):661–8. DOI: 10.1164/rccm.201001-0007OC

31. Zhao Q-H, Peng F-H, Wei H, He J, Chen F-D, Di R-M et al. Serum High-Density Lipoprotein Cholesterol Levels as a Prognostic Indicator in Patients With Idiopathic Pulmonary Arterial Hypertension. The American Journal of Cardiology. 2012;110(3):433–9. DOI: 10.1016/j.amjcard.2012.03.042

32. Zhang S, Yang T, Xu X, Wang M, Zhong L, Yang Y et al. Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study. BMC Pulmonary Medicine. 2015;15(1):50. DOI: 10.1186/s12890-015-0045-8

33. Giannakoulas G, Mouratoglou S-A, Gatzoulis MA, Karvounis H. Blood biomarkers and their potential role in pulmonary arterial hypertension associated with congenital heart disease. A systematic review. International Journal of Cardiology. 2014;174(3):618–23. DOI: 10.1016/j.ijcard.2014.04.156

34. Malhotra R, Paskin-Flerlage S, Zamanian RT, Zimmerman P, Schmidt JW, Deng DY et al. Circulating Angiogenic Modulatory Factors Predict Survival and Functional Class in Pulmonary Arterial Hypertension. Pulmonary Circulation. 2013;3(2):369–80. DOI: 10.4103/2045-8932.110445

35. Tiede SL, Gall H, Dörr O, Guilherme M dos S, Troidl C, Liebetrau C et al. New potential diagnostic biomarkers for pulmonary hypertension. European Respiratory Journal. 2015;46(5):1390–6. DOI: 10.1183/13993003.00187-2015

36. Damico R, Kolb TM, Valera L, Wang L, Housten T, Tedford RJ et al. Serum Endostatin Is a Genetically Determined Predictor of Survival in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine. 2015;191(2):208–18. DOI: 10.1164/rccm.201409-1742OC

37. Kümpers P, Nickel N, Lukasz A, Golpon H, Westerkamp V, Olsson KM et al. Circulating angiopoietins in idiopathic pulmonary arterial hypertension. European Heart Journal. 2010;31(18):2291– 300. DOI: 10.1093/eurheartj/ehq226

38. Langleben D, Orfanos SE, Giovinazzo M, Hirsch A, Baron M, Senécal J-L et al. Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension. Arthritis & Rheumatism. 2008;58(4):1156–64. DOI: 10.1002/art.23405

39. Orfanos SE, Psevdi E, Stratigis N, Langleben D, Catravas JD, Kyriakidis M et al. Pulmonary capillary endothelial dysfunction in early systemic sclerosis. Arthritis & Rheumatism. 2001;44(4):902– 11. DOI: 10.1002/1529-0131(200104)44:4<902::AIDANR147>3.3.CO;2-0

40. Langleben D, Orfanos SE, Giovinazzo M, Schlesinger RD, Hirsch AM, Blenkhorn F et al. Acute Vasodilator Responsiveness and Microvascular Recruitment in Idiopathic Pulmonary Arterial Hypertension. Annals of Internal Medicine. 2015;162(2):154–6. DOI: 10.7326/M14-1402

41. Nickel N, Kempf T, Tapken H, Tongers J, Laenger F, Lehmann U et al. Growth Differentiation Factor-15 in Idiopathic Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine. 2008;178(5):534–41. DOI: 10.1164/rccm.200802-235OC

42. Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS et al. Galectin-3, a Marker of Cardiac Fibrosis, Predicts Incident Heart Failure in the Community. Journal of the American College of Cardiology. 2012;60(14):1249–56. DOI: 10.1016/j.jacc.2012.04.053

43. Fenster BE, Lasalvia L, Schroeder JD, Smyser J, Silveira LJ, Buckner JK et al. Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension. Heart and Vessels. 2016;31(6):939–46. DOI: 10.1007/s00380-015-0691-z

44. Li LС, Li J, Gao J. Functions of Galectin-3 and Its Role in Fibrotic Diseases. Journal of Pharmacology and Experimental Therapeutics. 2014;351(2):336–43. DOI: 10.1124/jpet.114.218370

45. Nadadur RD, Umar S, Wong G, Eghbali M, Iorga A, Matori H et al. Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension. Journal of Applied Physiology. 2012;113(1):149–58. DOI: 10.1152/japplphysiol.01349.2011

46. Lorenzen JM, Nickel N, Krämer R, Golpon H, Westerkamp V, Olsson KM et al. Osteopontin in Patients With Idiopathic Pulmonary Hypertension. Chest. 2011;139(5):1010–7. DOI: 10.1378/chest.10-1146

47. Le Hiress M, Tu L, Ricard N, Phan C, Thuillet R, Fadel E et al. Proinflammatory Signature of the Dysfunctional Endothelium in Pulmonary Hypertension. Role of the Macrophage Migration Inhibitory Factor/CD74 Complex. American Journal of Respiratory and Critical Care Medicine. 2015;192(8):983–97. DOI: 10.1164/rccm.201402-0322OC

48. Stefanantoni K, Sciarra I, Vasile M, Badagliacca R, Poscia R, Pendolino M et al. Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Reumatismo. 2015;66(4):270–6. DOI: 10.4081/reumatismo.2014.774

49. Özpelit E, Akdeniz B, Özpelit ME, Tas S, Bozkurt S, Tertemiz KC et al. Prognostic value of neutrophil-to-lymphocyte ratio in pulmonary arterial hypertension. Journal of International Medical Research. 2015;43(5):661–71. DOI: 10.1177/0300060515589394

50. Olsson KM, Olle S, Fuge J, Welte T, Hoeper MM, Lerch C et al. CXCL13 in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respiratory Research. 2016;17(1):21. DOI: 10.1186/s12931-016-0336-5

51. Шайдаков Е. В., Евлахов В. И. Роль эндотелия в патогенезе хронической тромбо-эмболической лёгочной гипертензии. Ангиология и сосудистая хирургия. 2016;22(1):22-6

52. Sarrion I, Milian L, Juan G, Ramon M, Furest I, Carda C et al. Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a. Oxidative Medicine and Cellular Longevity. 2015;2015:792846. DOI: 10.1155/2015/792846

53. Paulin R, Sutendra G, Gurtu V, Dromparis P, Haromy A, Provencher S et al. A miR-208–Mef2 Axis Drives the Decom pensation of Right Ventricular Function in Pulmonary Hypertension. Circulation Research. 2015;116(1):56–69. DOI: 10.1161/CIRCRESAHA.115.303910

54. Reis GS, Augusto VS, Silveira APC, Jordão AA, Baddini-Martinez J, Neto OP et al. Oxidative-Stress Biomarkers in Patients with Pulmonary Hypertension. Pulmonary Circulation. 2013;3(4):856–61. DOI: 10.1086/674764

55. Cracowski J-L, Degano B, Chabot F, Labarère J, Schwedhelm E, Monneret D et al. Independent Association of Urinary F2-Isoprostanes With Survival in Pulmonary Arterial Hypertension. Chest. 2012;142(4):869–76. DOI: 10.1378/chest.11-1267

56. Sharma S, Umar S, Potus F, Iorga A, Wong G, Meriwether D et al. Apolipoprotein A-I Mimetic Peptide 4F Rescues Pulmonary Hypertension by Inducing MicroRNA-193-3p. Circulation. 2014;130(9):776–85. DOI: 10.1161/CIRCULATIONAHA.114.007405

57. Ross DJ, Hough G, Hama S, Aboulhosn J, Belperio JA, Saggar R et al. Proinflammatory High-Density Lipoprotein Results from Oxidized Lipid Mediators in the Pathogenesis of Both Idiopathic and Associated Types of Pulmonary Arterial Hypertension. Pulmonary Circulation. 2015;5(4):640–8. DOI: 10.1086/683695

58. Schumann C, Lepper PM, Frank H, Schneiderbauer R, Wibmer T, Kropf C et al. Circulating biomarkers of tissue remodelling in pulmonary hypertension. Biomarkers. 2010;15(6):523–32. DOI: 10.3109/1354750X.2010.492431

59. Hessel M, Steendijk P, den Adel B, Schutte C, van der Laarse A. Pressure Overload-induced Right Ventricular Failure is Associated with Re-expression of Myocardial Tenascin-C and Elevated Plasma Tenascin-C Levels. Cellular Physiology and Biochemistry. 2009;24(3–4):201–10. DOI: 10.1159/000233246

60. Mansoor JK, Schelegle ES, Davis CE, Walby WF, Zhao W, Aksenov AA et al. Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension. PLoS ONE. 2014;9(4):e95331. DOI: 10.1371/journal.pone.0095331


Рецензия

Для цитирования:


Гайнитдинова В.В., Авдеев С.Н. Новые биомаркеры легочной гипертензии. Кардиология. 2019;59(7):84-94. https://doi.org/10.18087/cardio.2019.7.10259

For citation:


Gaynitdinova V.V., Avdeev S.N. Novel Biomarkers of Pulmonary Hypertension. Kardiologiia. 2019;59(7):84-94. (In Russ.) https://doi.org/10.18087/cardio.2019.7.10259

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