cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2017.10.10039cardio-37Research ArticleСЕРДЕЧНАЯ НЕДОСТАТОЧНОСТЬПатогенетическая и прогностическая значимость ростовых факторов в развитии хронической сердечной недостаточностиPathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart FailureТепляковА. Т.TeplyakovA. T.noemail@neicon.ruБерезиковаЕ. Н.BerezikovaE. N.berezikova@ngs.ruШиловС. Н.ShilovS. N.noemail@neicon.ruГраковаЕ. В.GrakovaE. V.noemail@neicon.ruТоримЮ. Ю.TorimJu. Ju.noemail@neicon.ruЕфремовА. В.EfremovA. V.noemail@neicon.ruСафроновИ. Д.SafronovI. D.noemail@neicon.ruПустоветоваМ. Г.PustovetovaM. G.noemail@neicon.ruПоповаА. А.PopovaA. A.noemail@neicon.ruАндрияноваА. В.AndriyanovaA. V.noemail@neicon.ruФГБНУ «НИИ кардиологии», «Томский национальный исследовательский медицинский центр РАН»Россия“Research Institute of Cardiology”Russian FederationГБОУ ВПО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian FederationРАМРоссияNovosibirsk State Medical UniversityRussian Federation20171711201857102028Copyright © Kardiomag, 20182018KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/37

Цель исследования. Изучить роль ростовых факторов (фактора роста эндотелия сосудов - VEGF, тромбоцитарного фактора роста АВ - PDGF-АВ и основного фактора роста фибробластов - FGF basic) в развитии и прогрессировании хронической сердечной недостаточности (ХСН) у больных ишемической болезнью сердца (ИБС). Материалы и методы. Обследованы 94 пациента с ХСН. В группу контроля вошли 32 человека. В начале исследования и через 12 мес наблюдения в сыворотке крови определяли уровень факторов роста методом иммуноферментного анализа. Результаты. VEGF, PDGF-AB и FGF basic играют важную роль в патогенезе развития и прогрессирования ХСН у больных ИБС, определяя повышенный риск развития сердечно-сосудистых осложнений при данной патологии. Сывороточная активность ростовых факторов характеризует тяжесть и характер течения ХСН: снижение уровней VEGF и FGF basic и повышение концентрации PDGF-AB в плазме крови происходят по мере прогрессирования заболевания. Исходно низкий уровень экспрессии VEGF вне зависимости от пола пациентов, значимо низкий уровень FGF basic и достоверно высокий PDGF-AB у мужчин характеризуют неблагоприятный характер течения ХСН. Заключение. Установлена взаимосвязь уровней VEGF, PDGF-AB и FGF basic в сыворотке крови с тяжестью и характером течения ХСН.

Aim. To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). Materials and methods. We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. Results. VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient’s sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. Conclusion. A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

хроническая сердечная недостаточностьишемическая болезнь сердцаростовые факторыchronic heart failureischemic heart diseasegrowth factorsReferencesБеленков Ю.Н. ИБС как основная причина сердечной недостаточности. Сердечная недостаточность 2004;5:77-78Беленков Ю.Н. ИБС как основная причина сердечной недостаточности. Сердечная недостаточность 2004;5:77-78Фомин И. В. Эпидемиология хронической сердечной недостаточности в Российской Федерации. В. кн.: Агеев Ф. Т., Арутюнов Г. П., Беленков Ю. Н., Васюк Ю. А. Хроническая сердечная недостаточность. М: ГЭОТАР-Медиа 2010;7-77Фомин И. В. Эпидемиология хронической сердечной недостаточности в Российской Федерации. В. кн.: Агеев Ф. Т., Арутюнов Г. П., Беленков Ю. Н., Васюк Ю. А. Хроническая сердечная недостаточность. М: ГЭОТАР-Медиа 2010;7-77Rolande D.M., Fantini J.P., Cardinalli N.A. et al. Prognostic determinants of patients with chronic systolic heart failure secondary to systemic arterial hypertension. Arq Bras Cardiol 2012;98:76-84.Rolande D.M., Fantini J.P., Cardinalli N.A. et al. Prognostic determinants of patients with chronic systolic heart failure secondary to systemic arterial hypertension. Arq Bras Cardiol 2012;98:76-84.Liu L., Eisen H.J. Epidemiology of heart failure and scope of the problem. Cardiol Clin 2014;32(1):1-8.Liu L., Eisen H.J. Epidemiology of heart failure and scope of the problem. Cardiol Clin 2014;32(1):1-8.Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438:932-936.Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438:932-936.Christian F., Ansel P., Behzad O. FGF23 induces left ventricular hypertrophy. J. Clin Invest 2011;121(11):4393-4408.Christian F., Ansel P., Behzad O. FGF23 induces left ventricular hypertrophy. J. Clin Invest 2011;121(11):4393-4408.Frechette J.P., Martineau I., Gagnon G. Platelet rich plasmas: growth factor content and roles in wound healing. J. Dent Res 2005;84:434-439.Frechette J.P., Martineau I., Gagnon G. Platelet rich plasmas: growth factor content and roles in wound healing. J. Dent Res 2005;84:434-439.Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J. Physiol Cell Physiol 2001;280:1358-1366.Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J. Physiol Cell Physiol 2001;280:1358-1366.Chin B.S., Blann A.D., Gibbs C.R. et al. Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failure. Eur J. Clin Invest 2003;33:941-948.Chin B.S., Blann A.D., Gibbs C.R. et al. Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failure. Eur J. Clin Invest 2003;33:941-948.Zachary I., Mathur A., Yla-Herttuala S., Martin J. Vascular protection: a novel nonangiogenic cardiovascular role for VEGF. Arterioscler Thromb Vasc Biol 2000;20:1512-1520.Zachary I., Mathur A., Yla-Herttuala S., Martin J. Vascular protection: a novel nonangiogenic cardiovascular role for VEGF. Arterioscler Thromb Vasc Biol 2000;20:1512-1520.Stannard A.K., Khurana R., Evans I.M. et al. Vascular endothelial growth factor synergistically enhances induction of E-selectin by TNF-a. Arterioscler Thromb Vasc Biol 2007;27:494-502.Stannard A.K., Khurana R., Evans I.M. et al. Vascular endothelial growth factor synergistically enhances induction of E-selectin by TNF-a. Arterioscler Thromb Vasc Biol 2007;27:494-502.Гавриленко Т.И., Рыжкова Н.А., Пархоменко А.Н. Сосудистый эндотелиальный фактор роста в клинике внутренних заболеваний и его патогенетическое значение. Украинский кардиологический журнал 2011;4:87-95Гавриленко Т.И., Рыжкова Н.А., Пархоменко А.Н. Сосудистый эндотелиальный фактор роста в клинике внутренних заболеваний и его патогенетическое значение. Украинский кардиологический журнал 2011;4:87-95Kimura K., Hashiguchi T., Deguchi T. et al. Serum VEGF as a prognostic factor of atherosclerosis. Atherosclerosis 2007;194:182-188.Kimura K., Hashiguchi T., Deguchi T. et al. Serum VEGF as a prognostic factor of atherosclerosis. Atherosclerosis 2007;194:182-188.Fuchs S., Lavi I., Tzang O. et al. Intracoronary monocyte chemoattractant protein 1 and vascular endothelial growth factor levels are associated with necrotic core, calcium and fibrous tissue atherosclerotic plaque components: an intracoronary ultrasound radiofrequency study. Cardiology 2012;123:125-132.Fuchs S., Lavi I., Tzang O. et al. Intracoronary monocyte chemoattractant protein 1 and vascular endothelial growth factor levels are associated with necrotic core, calcium and fibrous tissue atherosclerotic plaque components: an intracoronary ultrasound radiofrequency study. Cardiology 2012;123:125-132.Namiki A., Brogi E., Kearney M. et al. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J. Biol Chem 1995;270:31189-31905.Namiki A., Brogi E., Kearney M. et al. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J. Biol Chem 1995;270:31189-31905.Tsutsumi Y., Losordo D.W. Double face of VEGF. Circulation 2005;112:1248-1250.Tsutsumi Y., Losordo D.W. Double face of VEGF. Circulation 2005;112:1248-1250.Washio T., Nomoto K., Watanabe I. et al. Relationship between plasma homocysteine levels and congestive heart failure in patients with acute myocardial infarction. Homocysteine and congestive heart failure. Int Heart J. 2011;52:224-228.Washio T., Nomoto K., Watanabe I. et al. Relationship between plasma homocysteine levels and congestive heart failure in patients with acute myocardial infarction. Homocysteine and congestive heart failure. Int Heart J. 2011;52:224-228.Xia J.H., Xie A.N., Zhang K.L. et al. The vascular endothelial growth factor expression and vascular regeneration in infarcted myocardium by skeletal muscle satellite cells. Chin Med J. 2006;119:117-121.Xia J.H., Xie A.N., Zhang K.L. et al. The vascular endothelial growth factor expression and vascular regeneration in infarcted myocardium by skeletal muscle satellite cells. Chin Med J. 2006;119:117-121.Vila V., Martinez-Sales V., Almenar L. et al. Inflammation, endothelial dysfunction and angiogenesis markers in chronic heart failure patients. Int J. Cardiol 2008;130(2):276-277.Vila V., Martinez-Sales V., Almenar L. et al. Inflammation, endothelial dysfunction and angiogenesis markers in chronic heart failure patients. Int J. Cardiol 2008;130(2):276-277.Holmes D.I., Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 2005;6:209-219.Holmes D.I., Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 2005;6:209-219.Andrae J., Gallini R., Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22:1276-1312.Andrae J., Gallini R., Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008;22:1276-1312.Tiyyagura S.R., Pinney S.P. Left ventricular remodeling after myocardial infarction: past, present, and future. Mt Sinai J. Med 2006;73:840-851.Tiyyagura S.R., Pinney S.P. Left ventricular remodeling after myocardial infarction: past, present, and future. Mt Sinai J. Med 2006;73:840-851.Dalal M., Sun K., Cappola A.R., Ferrucci L. et al. Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women. Eur J. Endocrinol 2011;165:797-803.Dalal M., Sun K., Cappola A.R., Ferrucci L. et al. Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women. Eur J. Endocrinol 2011;165:797-803.Christian F., Ansel P., Behzad O. FGF23 induces left ventricular hypertrophy. J. Clin Invest 2011;121:4393-4408.Christian F., Ansel P., Behzad O. FGF23 induces left ventricular hypertrophy. J. Clin Invest 2011;121:4393-4408.Grusona D., Lepoutreb T., Ketelslegersb J.M. et al. C-terminal FGF23 is a strong predictor of survival in systolic heart failure. Peptides 2012;37:258-262.Grusona D., Lepoutreb T., Ketelslegersb J.M. et al. C-terminal FGF23 is a strong predictor of survival in systolic heart failure. Peptides 2012;37:258-262.Plischke M., Neuhold S., Adlbrecht C., et al. Inorganic phosphate and FGF-23 predict outcome in stable systolic heart failure. Eur J. Clin Invest 2012;42:649-656.Plischke M., Neuhold S., Adlbrecht C., et al. Inorganic phosphate and FGF-23 predict outcome in stable systolic heart failure. Eur J. Clin Invest 2012;42:649-656.Shou M., Thirumurti V., Rajanayagam M. Effect of Basic Fibroblast Growth Factor on Myocardial Angiogenesis in Dogs With Mature Collateral Vessels. J. Am College Cardiol 1997;29:1102-1106.Shou M., Thirumurti V., Rajanayagam M. Effect of Basic Fibroblast Growth Factor on Myocardial Angiogenesis in Dogs With Mature Collateral Vessels. J. Am College Cardiol 1997;29:1102-1106.Collinson D., Donnelly R. Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J. Vasc Endovasc Surg 2004;28:9-23.Collinson D., Donnelly R. Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J. Vasc Endovasc Surg 2004;28:9-23.Saunders K.B., D'Amore P.A. FGF and TGF-beta actions and interactions in biological systems. Crit Rev Eukar Gene Experes 1991;3:165-172.Saunders K.B., D'Amore P.A. FGF and TGF-beta actions and interactions in biological systems. Crit Rev Eukar Gene Experes 1991;3:165-172.Conway E.M., Collen D., Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001;49:507-521.Conway E.M., Collen D., Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001;49:507-521.Sato K., Laham R.J., Pearlman J.D. et al. Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. Ann Thorac Surg 2000;70(6):2113-2118.Sato K., Laham R.J., Pearlman J.D. et al. Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. Ann Thorac Surg 2000;70(6):2113-2118.Blann A.D., Belgore F.M., McCollum C.N. et al. Vascular endothelial growth factor and its receptor, FLT-1, in the plasma of patients with coronary or peripheral atherosclerosis, or type II diabetes. Clin Sci 2002;102:187-194.Blann A.D., Belgore F.M., McCollum C.N. et al. Vascular endothelial growth factor and its receptor, FLT-1, in the plasma of patients with coronary or peripheral atherosclerosis, or type II diabetes. Clin Sci 2002;102:187-194.Lerman O.Z., Galiano R.D., Armour M. et al. Cellular Dysfunction in the Diabetic fibroblast: Impairment in migration, VEGF production and response to hypoxia. Am J. Pathol 2003;162(1):303-312.Lerman O.Z., Galiano R.D., Armour M. et al. Cellular Dysfunction in the Diabetic fibroblast: Impairment in migration, VEGF production and response to hypoxia. Am J. Pathol 2003;162(1):303-312.Waltenberger J. Impaired collateral vessel development in diabetes; potential mechanisms and therapuetic implications. Cardiovasc Res 2001;49:554-560.Waltenberger J. Impaired collateral vessel development in diabetes; potential mechanisms and therapuetic implications. Cardiovasc Res 2001;49:554-560.Kimura I., Honda R., Okai H., Okabe M. Vascular endothelial growth factor promotes cell-cycle transition from G0 to G1 phase in subcultured endothelial cells of diabetic rat thoracic aorta. Jpn J. Pharmacol 2000;83(l):47-55.Kimura I., Honda R., Okai H., Okabe M. Vascular endothelial growth factor promotes cell-cycle transition from G0 to G1 phase in subcultured endothelial cells of diabetic rat thoracic aorta. Jpn J. Pharmacol 2000;83(l):47-55.Lotze U., Heinke S., Fritzenwanger M., Krack A. Carvedilol inhibits platelet-derived growth factor-induced signal transduction in human cardiac fibroblasts. J. Cardiovasc Pharmacol 2002;39(4):576-589.Lotze U., Heinke S., Fritzenwanger M., Krack A. Carvedilol inhibits platelet-derived growth factor-induced signal transduction in human cardiac fibroblasts. J. Cardiovasc Pharmacol 2002;39(4):576-589.Freedman S.B., Isner J.M. Therapeutic angiogenesis for coronary artery disease. Ann Intern Med 2002;136:54-71.Freedman S.B., Isner J.M. Therapeutic angiogenesis for coronary artery disease. Ann Intern Med 2002;136:54-71.Беленков Ю. Н., Агеев Ф. Т., Мареев В. Ю., Савченко В. Г. Мобилизация стволовых клеток костного мозга в лечении больных с сердечной недостаточностью. Кардиология 2003;53(3):7-12Беленков Ю. Н., Агеев Ф. Т., Мареев В. Ю., Савченко В. Г. Мобилизация стволовых клеток костного мозга в лечении больных с сердечной недостаточностью. Кардиология 2003;53(3):7-12

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