ФИЗИОЛОГИЧЕСКАЯ И ПАТОФИЗИОЛОГИЧЕСКАЯ РОЛЬ СТИМУЛИРУЮЩЕГО ФАКТОРА РОСТА ST2

Аннотация

ST2 является членом семейства рецепторов интерлейкина 1 (IL-1) и состоит из двух изоформ: трансмембранной, или клеточной (ST2L), и растворимой, или циркулирующей (sST2). ST2 является рецептором IL-33, который представляет собой IL-1-подобный цитокин. IL-33 проявляет свои клеточные функции, связывая рецепторный комплекс, состоящий из вспомогательного белка ST2L и IL-1R. Система IL-33/ST2 активируется в кардиомиоцитах и фибробластах в ответ на механическое раздражение или повреждение. Было показано, что взаимодействие между IL-33 и ST2L является кардиопротективным. На экспериментальных моделях продемонстрировано уменьшение фиброза миокарда, предотвращение развития гипертрофии кардиомиоцитов, снижение апоптоза и улучшение функциональной способности миокарда при взаимодействии IL-33 и ST2L. Положительные эффекты IL-33, в частности, связаны с рецептором ST2L. В свою очередь sST2, связываясь с IL-33, приводит к блокированию взаимодействия между IL-33/ST2L, устраняя тем самым кардиопротективные эффекты. В последние годы знания о роли ST2 в патофизиологии сердечно-сосудистых заболеваний расширились, и роль ST2 связывают с дисфункцией миокарда, фиброзом и ремоделированием. Помимо своей миокардиальной роли, система IL-33/ST2 может играть дополнительную роль в развитии и прогрессировании атеросклероза. Система IL-33/ST2L может обладать терапевтическим потенциалом при миокардиальной перегрузке или травме. sST2, напротив, действует как ложный рецептор IL-33, блокируя кардиозащитные эффекты взаимодействия IL-33/ST2L.

Об авторах

Список литературы

Ho J.E., Sritara P., deFilippi C.R., Wang T.J. Soluble ST2 Testing in the General Population. Am. J. Cardiol. 2015; 115.

Stone N.J., Robinson J., Lichtenstein A.H., Merz C.N., Blum C.B., Eckel R.H. et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129(25 Suppl 2): S1e45.

Goff D.C. Jr., Lloyd-Jones D.M., Bennett G., Coady S., D’Agostino R.B. Sr., 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(25 Suppl 2): S49e73.

Khot U.N., Khot M.B., Bajzer C.T., Sapp S.K., Ohman E.M., Brener S.J. et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003; 290: 898e904.

Rose G. Strategy of prevention: lessons from cardiovascular disease. Br. Med. J. 1981; 282: 1847e1851.

Bayes-Genis A. ST2-Based Precision Medicine in Device Management: the Next Frontier Beyond MADIT-CRT? J. Cardiovasc. Transl. Res. 2016; 9(5-6): 419-20.

O’Donoghue M.L., Morrow D.A., Cannon C.P., Jarolim P., Desai N.R., Sherwood M.W. et al. Multimarker Risk Stratification in Patients With Acute Myocardial Infarction. J. Am. Heart. Assoc. 2016; 5: e002586.

Maisel A.S., Di Somma S. Dowe need another heart failure biomarker: focus on soluble suppression of tumorigenicity 2 (sST2). European Heart Journal. 2016; 0: 1-9. doi:10.1093/eurheartj/ehw462.

Maisel A.S., Richards A.M., Pascual-Figal D., Mueller C. Serial ST2 Testing in Hospitalized Patients With Acute Heart Failure. Am. J. Cardiol. 2015; 115(7): 32B-7B.

Kakkar R., Hei H., Dobner S., Lee R.T. Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J. Biol. Chem. 2012; 287: 6941e6948.

Kakkar R., Lee R.T. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat. Rev. Drug. Discov. 2008; 7(10): 827-40.

Sanada S., Hakuno D., Higgins L.J., Schreiter E.R., McKenzie A.N.J., Lee R.T. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J. Clin. Invest. 2007; 117(6): 1538-49.

Tominaga S. A putative protein of a growth specific cDNA from BALB/ c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett. 1989; 258: 301e304.

Klemenz R., Hoffmann S., Werenskiold A.K. Serum- and oncoproteinmediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc. Natl. Acad. Sci. USA. 1989; 86: 5708e5712.

Weinberg E.O., Shimpo M., De Keulenaer G.W., MacGillivray C., Tominaga S., Solomon S.D. et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002; 106: 2961e2966.

Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K. et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005; 23: 479e490.

Bergers G., Reikerstorfer A., Braselmann S., Graninger P., Busslinger M. Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. EMBO J. 1994; 13: 1176e1188.

Pascual-Figal D.A., Januzzi J.L. The Biology of ST2: The International ST2 Consensus Panel. Am. J. Cardiol. 2015; 115(7 Suppl): 3B-7B.

Baba Y., Maeda K., Yashiro T., Inage E., Kasakura K., Suzuki R. et al. GATA2 is a critical transactivator for the human IL1RL1/ST2 promoter in mast cells/basophils: opposing roles for GATA2 and GATA1 in human IL1RL1/ST2 gene expression. J. Biol. Chem. 2012; 287: 32689e32696.

Caporali A., Meloni M., Miller A.M., Vierlinger K., Cardinali A., Spinetti G. et al. Soluble ST2 is regulated by p75 neurotrophin receptor and predictsmortality in diabetic patients with critical limb ischemia. Arterioscler. Thromb. Vasc. Biol. 2012; 32: 149e160.

Ho J.E., Chen W.Y., Chen M.H., Larson M.G., McCabe E.L., Cheng S. et al. Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling. J. Clin. Invest. 2013; 123(10): 4208-18.

Chackerian A.A., Oldham E.R., Murphy E.E., Schmitz J., Pflanz S., Kastelein R.A. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J. Immunol. 2007; 179: 2551e2555.

Daniels L.B., Bayes-Genis A. Using ST2 in cardiovascular patients: a review. Future Cardiology. 2014; 10: 525-39.

Schmieder A., Multhoff G., Radons J. Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells. Cytokine. 2012; 60: 514e521.

Komai-Koma M., Xu D., Li Y., McKenzie A.N., McInnes I.B., Liew F.Y. IL-33 is a chemoattractant for human Th2 cells. Eur. J. Immunol. 2007; 37: 2779-86.

Kropf P., Herath S., Tewari R., Syed N., Klemenz R., Müller I. Identification of two distinct subpopulations of Leishmania major-specific T helper 2 cells. Infect. Immun. 2002; 70: 5512-20.

Hoshino K., Kashiwamura S., Kuribayashi K., Kodama T., Tsujimura T., Nakanishi K. et al. The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function. J. Exp. Med. 1999; 190: 1541-8.

Townsend M.J., Fallon P.G., Matthews D.J., Jolin H.E., McKenzie A.N. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J. Exp. Med. 2000; 191: 1069-76.

Sanchez-Mas J., Lax A., Asensio-Lopez M., Fernandez-Del Palacio M., Caballero L., Santarelli G. et al. Modulation of IL-33/ST2 system in post-infarction heart failure: correlation with cardiac remodeling markers. Eur. J. Clin. Invest. 2014; 44(7): 643-51.

Weir R.A.P., Miller A.M., Murphy G.E.J., Clements S., Steedman T., Connell J.M.C. et al. Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction. J. Am. Coll. Cardiol. 2010; 55: 243e250.

Shah R.V., Chen-Tournoux A.A., Picard M.H., vanKimmenade R.R.J., Januzzi J.L. Serum levels of the interleukin-1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea. Circ. Heart. Fail. 2009; 2: 311e319.

Januzzi J.L., Peacock W.F., Maisel A.S., Chae C.U., Jesse R.L., Baggish A.L. 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: 607e613.

Barbarash O., Gruzdeva O., Uchasova E., Dyleva Y., Belik E., Akbasheva O., Karetnikova V., Shilov A. Prognostic Value of Soluble ST2 During Hospitalization for ST-Segment Elevation Myocardial Infarction. Ann. Lab. Med. 2016; 36(4): 313-9.

Дылева Ю.А., Груздева О.В., Акбашева О.Е., Учасова Е.Г., Федорова Н.В., Чернобай А.Г., Каретникова В.Н., Косарева С.Н., Кашталап В.В., Федорова Т.С., Барбараш О.Л. Значение стимулирующего фактора роста ST2 и NT-proBNP в оценке постинфарктного ремоделирования сердца. Российский кардиологический журнал. 2015; 12(128): 63-71

Seki K., Sanada S., Kudinova A.Y., Steinhauser M.L., Handa V., Gannon J. et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ. Heart. Fail. 2009; 2: 684e691.

Yndestad A., Marshall A.K., Hodgkinson J.D., Tham E.L., Sugden P.H., Clerk A. Modulation of interleukin signalling and gene expression in cardiac myocytes by endothelin-1. Int. J. Biochem. Cell. Biol. 2010; 42: 263e272.

Lax A., Sanchez-Mas J., Asensio-Lopez M., Fernandez-Del Palacio M., Caballero L., Garrido I. et al. Mineralocorticoid receptor antagonists modulate galectin-3 and IL-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction. JACC Heart Fail. 2015; 3: 50e58.

Bartunek J., Delrue L., Van Durme F., Muller O., Casselman F., De Wiest B. et al. Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J. Am. Coll. Cardiol. 2008; 52: 2166e2174.

Demyanets S., Kaun C., Pentz R., Krychtiuk K.A., Rauscher S., Pfaffenberger S. et al. Components of the interleukin-33/ST2 systemare differentially expressed and regulated in human cardiac cells and in cells of the cardiac vasculature. J. Mol. Cell. Cardiol. 2013; 60: 16e26.

Miller A.M., Xu D., Asquith D.L., Denby L., Li Y., Sattar N. et al. IL-33 reduces the development of atherosclerosis. J. Exp. Med. 2008; 205: 339e346.

Dieplinger B., Januzzi J.L. Jr., 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: 33e40.

Coglianese E.E., Larson M.G., Vasan R.S., Ho J.E., Ghorbani A., McCabe E.L. et al. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study. Clin. Chem. 2012; 58: 1673e1681.

Fousteris E., Melidonis A., Panoutsopoulos G., Tzirogiannis K., Foussas S., Theodosis-Georgilas A. et al. Toll/interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction. Cardiovasc. Diabetol. 2011; 10: 101e108.

Miller A.M., Purves D., McConnachie A., Asquith D.L., Batty G.D., Burns H. et al. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes? PLoS One. 2012; 7: e47830.

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: 1431e1436.

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: 1596e1604.

Chen L.Q., de Lemos J.A., Das S.R., Ayers C.R., Rohatgi A. Soluble ST2 is associated with all-cause and cardiovascular mortality in a populationbased cohort: the Dallas Heart Study. Clin. Chem. 2013; 59: 536e546.

Ginsberg E., Seliger S., Gottdiener J.S., Christenson R., End C., DeFilippi C. Soluble ST2 predicts incident heart failure and cardiovascular death in older adults. J. Am. Coll. Cardiol. 2014; 63: A768.

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