arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2013-19-2-148-155arthyper-115Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLEГИПЕРТРОФИЧЕСКАЯ КАРДИОМИОПАТИЯ: ФИБРОЗ ИЛИ ГИПЕРТРОФИЯHYPERTROPHIC CARDIOMYOPATHY: FIBROSIS OR HYPERTROPHYСавченкоМ. И.SavchenkoM. I.

Ассистент кафедры факультетской терапии ГБОУ ВПО СПб ГПМУ, врач-кардиолог СПб ГБУЗ «Городская больница № 46».

Контактная информация: Учебный пер., д. 5, Санкт-Петербург, Россия, 194354. Тел.: 8 (904) 338–01–22. E-mail: savchenko_m@yahoo.com (Савченко Маргарита Ильинична).

Corresponding author: 5 Uchebniy lane, St Petersburg, Russia, 194354. E-mail: savchenko_m@yahoo.com (Margarita I. Savchenko, MD, an Assistant at the St Petersburg State Pediatric Academy, а Cardiologist at the State hospital № 46).

savchenko_m@yahoo.comКовалевЮ. Р.KovalevYU. R.

Доктор медицинских наук, профессор, заведующий кафедрой факультетской терапии ГОУ ВПО СПб ГПМУ

savchenko_m@yahoo.comКучинскийА. П.KuchinskiyA. P.

Кандидат медицинских наук, доцент кафедры факультетской терапии ГБОУ ВПО СПб ГПМУ, заведующий отделением кардиологии № 1 СПб ГБУЗ «Городская многопрофильная больница № 2»

savchenko_m@yahoo.comСанкт-Петербургский государственный педиатрический медицинский университет, Санкт-Петербург; Городская больница № 46», Санкт-ПетербургРоссияSt Petersburg State Pediatric Academy, St Petersburg; State hospital № 46, St Petersburg, RussiaRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет, Санкт-ПетербургРоссияSt Petersburg State Pediatric Academy, St PetersburgRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет, Санкт-Петербург; Городская многопрофильная больница № 2», Санкт-ПетербургРоссияSt Petersburg State Pediatric Academy, St Petersburg; City hospital № 2, St Petersburg, RussiaRussian Federation201328042013192148155Copyright © Савченко М.И., Ковалев Ю.Р., Кучинский А.П., 20132013Савченко М.И., Ковалев Ю.Р., Кучинский А.П.Savchenko M.I., Kovalev Y.R., Kuchinskiy A.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/115

Гипертрофическая кардиомиопатия, несмотря на свою довольно частую встречаемость — 0,2 % или 1:500 в популяции, остается одним из самых загадочных и не расшифрованных до конца заболеваний миокарда. Коварство заболевания и в том, что оно не имеет ни специфических анатомических и гистоморфологических проявлений, ни динамики клинических проявлений и по сути является миной замедленного действия: когда именно и в какой клинической форме проявит себя, предсказать невозможно. Клинический фенотип варьирует от латентного течения и отсутствия симптомов на протяжении всей жизни до быстрого прогрессирования сердечной недостаточности или внезапной сердечной смерти из-за тяжелых нарушений ритма. В обзоре отражены современные представления о генетике, гистоморфологии и патогенезе заболевания.

Objective. Despite the high frequency — 0,2 % (1:500) population, hypertrophic cardiomyopathy (HCM) is still considered one of the most mysterious and misunderstood diseases of myocardium. Insidious pathology has neither specific anatomical and morphological, nor clinical features which makes it a delayed-action bomb: nobody is capable to predict when and what clinical symptoms develop. The clinical phenotype of HCM varies from latent course when the symptoms are absent till rapid progress of heart failure syndrome and sudden cardiac death due to severe arrhythmia. The review covers modern view on genetics, morphology and pathogenesis of HCM.

гипертрофическая кардиомиопатиягипертрофияфиброзполиморфизмыhypertrophic cardiomyopathyhypertrophyfibrosispolymorphismsReferencesMaron B.J., Gardin J.M., Flack J.M., Gidding S.S. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA Study // Circulation. — 1995. — Vol. 92, № 4. — Р. 785–789.Maron B.J., Gardin J.M., Flack J.M., Gidding S.S. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA Study // Circulation. — 1995. — Vol. 92, № 4. — Р. 785–789.McLeod C.J., Bos J.M., Theis J.L. et al. Histologic characterization of hypertrophic cardiomyopathy with and without myofi lament mutations // Am. Heart J. — 2009. — Vol. 158, № 5. — Р. 799–805.McLeod C.J., Bos J.M., Theis J.L. et al. Histologic characterization of hypertrophic cardiomyopathy with and without myofi lament mutations // Am. Heart J. — 2009. — Vol. 158, № 5. — Р. 799–805.Shirani J., Pick R., Roberts W.C., Maron B.J. Morphology and signifi cance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death // J. Am. Coll. Cardiol. — 2000. — Vol. 35, № 1. — Р. 36–44.Shirani J., Pick R., Roberts W.C., Maron B.J. Morphology and signifi cance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death // J. Am. Coll. Cardiol. — 2000. — Vol. 35, № 1. — Р. 36–44.Watkins H., McKenna W.J., Thierfelder L. et al. Mutations in the genes for cardiac troponin T and α-tropomyosin in hypertrophic cardiomyopathy // N. Engl. J. Med. — 1995. — Vol. 332, № 16. — Р. 1058–1065.Watkins H., McKenna W.J., Thierfelder L. et al. Mutations in the genes for cardiac troponin T and α-tropomyosin in hypertrophic cardiomyopathy // N. Engl. J. Med. — 1995. — Vol. 332, № 16. — Р. 1058–1065.Frey N., Luedde M., Katus H.A. Mechanisms of disease: hypertrophic cardiomyopathy // Nature Rev. Cardiol. — 2011. — Vol. 9, № 2. — Р. 91–100.Frey N., Luedde M., Katus H.A. Mechanisms of disease: hypertrophic cardiomyopathy // Nature Rev. Cardiol. — 2011. — Vol. 9, № 2. — Р. 91–100.Alcalai R., Seidman J.G., Seidman C.E. Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics // J. Cardiovasc. Electrophysiol. — 2008. — Vol. 19, № 1. — Р. 104–110.Alcalai R., Seidman J.G., Seidman C.E. Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics // J. Cardiovasc. Electrophysiol. — 2008. — Vol. 19, № 1. — Р. 104–110.Gersh B.J., Maron B.J., Bonow R.O. et al. 2011 ACCF/ AHA Guideline for the diagnosis and treatment of hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 2011. — Vol. 58, № 25. — Р. e212–260.Gersh B.J., Maron B.J., Bonow R.O. et al. 2011 ACCF/ AHA Guideline for the diagnosis and treatment of hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 2011. — Vol. 58, № 25. — Р. e212–260.Ho C.Y. Genetics and clinical destiny: improving care in hypertrophic cardiomyopathy // Circulation. — 2010. — Vol. 122, № 23. — Р. 2430–2440.Ho C.Y. Genetics and clinical destiny: improving care in hypertrophic cardiomyopathy // Circulation. — 2010. — Vol. 122, № 23. — Р. 2430–2440.Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counseling // J. Med. Genet. — 2005. — Vol. 42, № 10. — Р. e59.Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counseling // J. Med. Genet. — 2005. — Vol. 42, № 10. — Р. e59.Girolami F., Ho C.Y., Semsarian C. et al. Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations // J. Am. Coll. Cardiol. — 2010. — Vol. 55, № 14. — Р. 1444–1453.Girolami F., Ho C.Y., Semsarian C. et al. Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations // J. Am. Coll. Cardiol. — 2010. — Vol. 55, № 14. — Р. 1444–1453.Ho C.Y., Lever H.M., DeSanctis R., Farver C.F., Seidman J.G., Seidman C.E. Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy // Circulation. — 2000. — Vol. 102, № 16. — Р. 1950–1955.Ho C.Y., Lever H.M., DeSanctis R., Farver C.F., Seidman J.G., Seidman C.E. Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy // Circulation. — 2000. — Vol. 102, № 16. — Р. 1950–1955.Force T., Bonow R.O., Houser S.R. et al. Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung, and Blood Institute. Jefferson Digital Commons // Circulation. — 2010. — Vol. 122, № 11. — Р. 1130–1133.Force T., Bonow R.O., Houser S.R. et al. Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung, and Blood Institute. Jefferson Digital Commons // Circulation. — 2010. — Vol. 122, № 11. — Р. 1130–1133.Holweg C.T., Baan C.C., Niesters H.G. et al. TGF-beta1 gene polymorphisms in patients with end-stage heart failure // J. Heart Lung Transplantation. — 2001. — Vol. 20, № 9. — Р. 979–984.Holweg C.T., Baan C.C., Niesters H.G. et al. TGF-beta1 gene polymorphisms in patients with end-stage heart failure // J. Heart Lung Transplantation. — 2001. — Vol. 20, № 9. — Р. 979–984.Tester D.J., Ackerman M.J. Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice // Circulation. — 2011. — Vol. 123, № 9. — Р. 1021–1037.Tester D.J., Ackerman M.J. Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice // Circulation. — 2011. — Vol. 123, № 9. — Р. 1021–1037.Ahmad F., Seidman J.G., Seidman C.E. The genetic basis for cardiac remodeling // Ann. Rev. Genomics Hum. Gen. — 2005. — Vol. 6. — P. 185–216.Ahmad F., Seidman J.G., Seidman C.E. The genetic basis for cardiac remodeling // Ann. Rev. Genomics Hum. Gen. — 2005. — Vol. 6. — P. 185–216.Frey N., Franz W.M., Gloeckner K. et al. Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias // Cardiovasc. Res. — 2000. — Vol. 47, № 2. — Р. 254–264.Frey N., Franz W.M., Gloeckner K. et al. Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias // Cardiovasc. Res. — 2000. — Vol. 47, № 2. — Р. 254–264.Thierfelder L., Watkins H., MacRae C. et al. α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere // Cell. — 1994. — Vol. 77, № 5. — Р. 701–712.Thierfelder L., Watkins H., MacRae C. et al. α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere // Cell. — 1994. — Vol. 77, № 5. — Р. 701–712.Erdmann J., Raible J., Maki-Abadi J. et al. Spectrum of clinical phenotypes and gene variants in cardiac myosinbinding protein C mutation carriers with hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 2001. — Vol. 38, № 2. — Р. 322–330.Erdmann J., Raible J., Maki-Abadi J. et al. Spectrum of clinical phenotypes and gene variants in cardiac myosinbinding protein C mutation carriers with hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 2001. — Vol. 38, № 2. — Р. 322–330.Oliva-Sandoval M.J., Ruiz-Espejo F., Monserrat L. et al. Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3 // Heart (Br. Cardiac Soc.). — 2010. — Vol. 96, № 24. — Р. 1980–1984.Oliva-Sandoval M.J., Ruiz-Espejo F., Monserrat L. et al. Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3 // Heart (Br. Cardiac Soc.). — 2010. — Vol. 96, № 24. — Р. 1980–1984.Roberts C.S., Roberts W.C. Morphologic features / In: Zipes D.P., Rowlands D.J. (eds). Progress in Cardiology 2/2. — Philadelphia: Lea & Febiger, 1989. — Р. 3–32.Roberts C.S., Roberts W.C. Morphologic features / In: Zipes D.P., Rowlands D.J. (eds). Progress in Cardiology 2/2. — Philadelphia: Lea & Febiger, 1989. — Р. 3–32.Maron B.J., Roberts W.C. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy // Circulation. — 1979. — Vol. 59, № 4. — Р. 689–706.Maron B.J., Roberts W.C. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy // Circulation. — 1979. — Vol. 59, № 4. — Р. 689–706.Maron B.J., Wolfson J.K., Roberts W.C. Relation between extent of cardiac muscle cell disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1992. — Vol. 70, № 7. — Р. 785–790.Maron B.J., Wolfson J.K., Roberts W.C. Relation between extent of cardiac muscle cell disorganization and left ventricular wall thickness in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1992. — Vol. 70, № 7. — Р. 785–790.Tanaka M., Fujiwara H., Onodera T. et al. Morphological features of hypertrophic cardiomyopathy with congestive heart failure and a small left ventricular cavity // Japanese Circulation J. — 1997. — Vol. 51, № 6. — Р. 647–650.Tanaka M., Fujiwara H., Onodera T. et al. Morphological features of hypertrophic cardiomyopathy with congestive heart failure and a small left ventricular cavity // Japanese Circulation J. — 1997. — Vol. 51, № 6. — Р. 647–650.Maron B.J., Shen W.K., Link M.S. et al. Effi cacy of implantable cardioverter-defi brillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy // N. Engl. J. Med. — 2000. — Vol. 342, № 6. — Р. 365–373.Maron B.J., Shen W.K., Link M.S. et al. Effi cacy of implantable cardioverter-defi brillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy // N. Engl. J. Med. — 2000. — Vol. 342, № 6. — Р. 365–373.Olivetti G., Abbi R., Quaini F. et al. Apoptosis in the failing human heart // N. Engl. J. Med. — 1997. — Vol. 336, № 16. — Р. 1131–1141.Olivetti G., Abbi R., Quaini F. et al. Apoptosis in the failing human heart // N. Engl. J. Med. — 1997. — Vol. 336, № 16. — Р. 1131–1141.Kavantzas N.G., Lazaris A.C.H., Agapitos E.V., Nanas J., Davaris P.S. Histological assessment of apoptotic cell death in cardiomyopathies // Pathology. — 2000. — Vol. 32, № 3. — Р. 176–180.Kavantzas N.G., Lazaris A.C.H., Agapitos E.V., Nanas J., Davaris P.S. Histological assessment of apoptotic cell death in cardiomyopathies // Pathology. — 2000. — Vol. 32, № 3. — Р. 176–180.Maron B.J., Spirito P. Implications of left ventricular remodeling in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1998. — Vol. 81, № 11. — Р. 1339–1344.Maron B.J., Spirito P. Implications of left ventricular remodeling in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1998. — Vol. 81, № 11. — Р. 1339–1344.Kajstura J., Mansukhani M., Cheng W., Reiss K. Programmed cell death and expression of the protooncogene bcl-2 in myocytes during postnatal maturation of the heart // Exp. Cell Res. — 1995. — Vol. 219, № 1. — P. 110.Kajstura J., Mansukhani M., Cheng W., Reiss K. Programmed cell death and expression of the protooncogene bcl-2 in myocytes during postnatal maturation of the heart // Exp. Cell Res. — 1995. — Vol. 219, № 1. — P. 110.Cheng W., Li B., Kajstura J. et al. Stretch-induced programmed myocyte cell death // J. Clin. Invest. — 1995. — Vol. 96, № 5. — P. 2247–2259.Cheng W., Li B., Kajstura J. et al. Stretch-induced programmed myocyte cell death // J. Clin. Invest. — 1995. — Vol. 96, № 5. — P. 2247–2259.Ino T., Nishimoto K., Okubo M. et al. Apoptosis as a possible cause of wall thinning in end-stage HCM // Am. J. Cardiol. — 1997. — Vol. 79, № 8. — Р. 1137–1141.Ino T., Nishimoto K., Okubo M. et al. Apoptosis as a possible cause of wall thinning in end-stage HCM // Am. J. Cardiol. — 1997. — Vol. 79, № 8. — Р. 1137–1141.Maron B.J. Hypertrophic cardiomyopathy // Lancet. — 1997. — Vol. 350, № 9071. — P. 127–133.Maron B.J. Hypertrophic cardiomyopathy // Lancet. — 1997. — Vol. 350, № 9071. — P. 127–133.Maron B.J., Wolfson J.K., Epstein S.E., Roberts W.C. Intramural («small vessel») coronary artery disease in hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 1986. — Vol. 8, № 3. — Р. 545–557.Maron B.J., Wolfson J.K., Epstein S.E., Roberts W.C. Intramural («small vessel») coronary artery disease in hypertrophic cardiomyopathy // J. Am. Coll. Cardiol. — 1986. — Vol. 8, № 3. — Р. 545–557.Teekakirikul P., Eminaga S., Toka O. et al. Cardiac fi brosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-β // J. Clin. Invest. — 2010. — Vol. 120, № 10. — Р. 3520–3529.Teekakirikul P., Eminaga S., Toka O. et al. Cardiac fi brosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-β // J. Clin. Invest. — 2010. — Vol. 120, № 10. — Р. 3520–3529.Petrov V.V., Lijnen P.J., Fagard R.H. Stimulation of collagen production by TGF-beta 1 during differenatiation of cardiac fi broblasts to myofi bro-blasts // Am. J. Hypertens. — 2002. — Suppl. 1, № 15. — Р. 4.Petrov V.V., Lijnen P.J., Fagard R.H. Stimulation of collagen production by TGF-beta 1 during differenatiation of cardiac fi broblasts to myofi bro-blasts // Am. J. Hypertens. — 2002. — Suppl. 1, № 15. — Р. 4.Vaughan M.B., Howard E.W., Tomasek J.J. Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofi broblast // Exp. Cell Res. — 2000. — Vol. 257, № 1. — Р. 180–189.Vaughan M.B., Howard E.W., Tomasek J.J. Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofi broblast // Exp. Cell Res. — 2000. — Vol. 257, № 1. — Р. 180–189.Schwachula A., Riemann D., Kehlen A., Langner J. Characterization of the immunophenotype and functional properties of fi broblast-like synoviocytes in comparison to skin fi broblasts and umbilical vein endothelial cells // Immunobiology. — 1994. — Vol. 190, № 1. — Р. 67–92.Schwachula A., Riemann D., Kehlen A., Langner J. Characterization of the immunophenotype and functional properties of fi broblast-like synoviocytes in comparison to skin fi broblasts and umbilical vein endothelial cells // Immunobiology. — 1994. — Vol. 190, № 1. — Р. 67–92.Hinglais N., Heudes D., Nicoletti A. et al. Colocalization of myocardial fi brosis and infl ammatory cells in rats // J. Tech. Methods Pathol. — 1994. — Vol. 70, № 2. — Р. 286–294.Hinglais N., Heudes D., Nicoletti A. et al. Colocalization of myocardial fi brosis and infl ammatory cells in rats // J. Tech. Methods Pathol. — 1994. — Vol. 70, № 2. — Р. 286–294.Kagitani S., Ueno H., Hirade S., Takahashi T., Takata M., Inoue H. Tranilast attenuates myocardial fi brosis in association with suppression of monocyte/macrophage infi ltration in DOCA/ salt hypertensive rats // J. Hypertens. — 2004. — Vol. 22, № 5. — Р. 1007–1015.Kagitani S., Ueno H., Hirade S., Takahashi T., Takata M., Inoue H. Tranilast attenuates myocardial fi brosis in association with suppression of monocyte/macrophage infi ltration in DOCA/ salt hypertensive rats // J. Hypertens. — 2004. — Vol. 22, № 5. — Р. 1007–1015.Li G., Borger M.A., Williams W.G. et al. Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy // J. Thorac. Cardiovasc. Surg. — 2002. — Vol. 123, № 1. — Р. 89–95.Li G., Borger M.A., Williams W.G. et al. Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy // J. Thorac. Cardiovasc. Surg. — 2002. — Vol. 123, № 1. — Р. 89–95.Li G., Li R.K., Mickle D.A. et al. Elevated insulin-like growth factor-I and transforming growth factor-beta 1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy. A possible mechanism // Circulation. — 1998. — Vol. 98, № 19. — Р. 144–149.Li G., Li R.K., Mickle D.A. et al. Elevated insulin-like growth factor-I and transforming growth factor-beta 1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy. A possible mechanism // Circulation. — 1998. — Vol. 98, № 19. — Р. 144–149.Kupfahl C., Pink D., Friedrich K. et al. Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart // Cardiovasc. Res. — 2000. — Vol. 46, № 3. — Р. 463– 475.Kupfahl C., Pink D., Friedrich K. et al. Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart // Cardiovasc. Res. — 2000. — Vol. 46, № 3. — Р. 463– 475.Kim S., Ohta K., Hamaguchi A., Yukimura T. Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats // Hypertens. Dallas. — 1995. — Vol. 25, № 6. — Р. 1252.Kim S., Ohta K., Hamaguchi A., Yukimura T. Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats // Hypertens. Dallas. — 1995. — Vol. 25, № 6. — Р. 1252.Schultz J.J., Witt S.A., Glascock B.J. et al. TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II // J. Clin. Invest. — 2002. — Vol. 109, № 6. — Р. 787–796.Schultz J.J., Witt S.A., Glascock B.J. et al. TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II // J. Clin. Invest. — 2002. — Vol. 109, № 6. — Р. 787–796.Laviades C., Varo N., Di ez J. Transforming growth factor beta in hypertensives with cardiorenal damage // Hypertension. — 2000. — Vol. 36, № 4. — Р. 517–522.Laviades C., Varo N., Di ez J. Transforming growth factor beta in hypertensives with cardiorenal damage // Hypertension. — 2000. — Vol. 36, № 4. — Р. 517–522.Awad M.R., El-Gamel A., Hasleton P. et al. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation // Transplantation. — 1998. — Vol. 66, № 8. — Р. 1014–1020.Awad M.R., El-Gamel A., Hasleton P. et al. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation // Transplantation. — 1998. — Vol. 66, № 8. — Р. 1014–1020.Nordstro m P., Glader C.A., Dahle n G. et al. Oestrogen receptor alpha; gene polymorphism is related to aortic valve sclerosis in postmenopausal women // J. Int. Med. — 2003. — Vol. 254, № 2. — Р. 140–146.Nordstro m P., Glader C.A., Dahle n G. et al. Oestrogen receptor alpha; gene polymorphism is related to aortic valve sclerosis in postmenopausal women // J. Int. Med. — 2003. — Vol. 254, № 2. — Р. 140–146.Koch W., Hoppmann P., Mueller J.C., Scho mig A., Kastrati A. Association of transforming growth factor-beta1 gene polymorphisms with myocardial infarction in patients with angiographically proven coronary heart disease // Arterioscl. Thromb. Vasc. Biol. — 2006. — Vol. 26, № 5. — Р. 1114–1119.Koch W., Hoppmann P., Mueller J.C., Scho mig A., Kastrati A. Association of transforming growth factor-beta1 gene polymorphisms with myocardial infarction in patients with angiographically proven coronary heart disease // Arterioscl. Thromb. Vasc. Biol. — 2006. — Vol. 26, № 5. — Р. 1114–1119.Crobu F., Palumbo L., Franco E. et al. Role of TGF-beta1 haplotypes in the occurrence of myocardial infarction in young Italian patients // BMC Med. Genet. — 2008. — Vol. 9. — P. 13.Crobu F., Palumbo L., Franco E. et al. Role of TGF-beta1 haplotypes in the occurrence of myocardial infarction in young Italian patients // BMC Med. Genet. — 2008. — Vol. 9. — P. 13.Sie M.P., Uitterlinden A.G., Bos M.J. et al. TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study // Stroke. — 2006. — Vol. 37, № 11. — Р. 2667–2671.Sie M.P., Uitterlinden A.G., Bos M.J. et al. TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study // Stroke. — 2006. — Vol. 37, № 11. — Р. 2667–2671.Suthanthiran M., Li B., Song J.O. et al. Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage // Proc. Natl. Acad. Sci. U.S.A. — 2000. — Vol. 97, № 7. — Р. 3479–3484.Suthanthiran M., Li B., Song J.O. et al. Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage // Proc. Natl. Acad. Sci. U.S.A. — 2000. — Vol. 97, № 7. — Р. 3479–3484.Mallat Z., Gojova A., Marchiol-Fournigault C. et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice // Circ. Res. — 2001. — Vol. 89, № 10. — Р. 930–934.Mallat Z., Gojova A., Marchiol-Fournigault C. et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice // Circ. Res. — 2001. — Vol. 89, № 10. — Р. 930–934.Yokota M., Ichihara S., Lin T.L., Nakashima N., Yamada Y. Association of a T29-->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese // Circulation. — 2000. — Vol. 101, № 24. — Р. 2783–2787.Yokota M., Ichihara S., Lin T.L., Nakashima N., Yamada Y. Association of a T29-->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese // Circulation. — 2000. — Vol. 101, № 24. — Р. 2783–2787.Chou H.T., Chen C.H., Tsai C.H., Tsai F.J. Association between transforming growth factor-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease // Am. Heart J. — 2004. — Vol. 148, № 1. — Р. 181–186.Chou H.T., Chen C.H., Tsai C.H., Tsai F.J. Association between transforming growth factor-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease // Am. Heart J. — 2004. — Vol. 148, № 1. — Р. 181–186.Xu H.-Y., Hou X.-W., Wang L.-F., Wang N.-F., Xu J. Association between transforming growth factor β1 polymorphisms and left ventricle hypertrophy in essential hypertensive subjects // Mol. Cell. Biochem. — 2010. — Vol. 335, № 1-2. — P. 13–17.Xu H.-Y., Hou X.-W., Wang L.-F., Wang N.-F., Xu J. Association between transforming growth factor β1 polymorphisms and left ventricle hypertrophy in essential hypertensive subjects // Mol. Cell. Biochem. — 2010. — Vol. 335, № 1-2. — P. 13–17.Rao M., Guo D., Jaber B.L., Tighiouart H., Pereira B.J.G., Balakrishnan V.S. Transforming growth factor-beta 1 gene polymorphisms and cardiovascular disease in hemodialysis patients // Kidney Intern. — 2004. — Vol. 66, № 1. — Р. 419– 427.Rao M., Guo D., Jaber B.L., Tighiouart H., Pereira B.J.G., Balakrishnan V.S. Transforming growth factor-beta 1 gene polymorphisms and cardiovascular disease in hemodialysis patients // Kidney Intern. — 2004. — Vol. 66, № 1. — Р. 419– 427.

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