Статья
ГИПЕРТРОФИЧЕСКАЯ КАРДИОМИОПАТИЯ: ФИБРОЗ ИЛИ ГИПЕРТРОФИЯ
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.
1. 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.
2. 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.
3. 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.
4. 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.
5. Frey N., Luedde M., Katus H.A. Mechanisms of disease: hypertrophic cardiomyopathy // Nature Rev. Cardiol. — 2011. — Vol. 9, № 2. — Р. 91–100.
6. 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.
7. 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.
8. Ho C.Y. Genetics and clinical destiny: improving care in hypertrophic cardiomyopathy // Circulation. — 2010. — Vol. 122, № 23. — Р. 2430–2440.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. Maron B.J., Spirito P. Implications of left ventricular remodeling in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1998. — Vol. 81, № 11. — Р. 1339–1344.
28. 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.
29. Cheng W., Li B., Kajstura J. et al. Stretch-induced programmed myocyte cell death // J. Clin. Invest. — 1995. — Vol. 96, № 5. — P. 2247–2259.
30. 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.
31. Maron B.J. Hypertrophic cardiomyopathy // Lancet. — 1997. — Vol. 350, № 9071. — P. 127–133.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. Laviades C., Varo N., Di ez J. Transforming growth factor beta in hypertensives with cardiorenal damage // Hypertension. — 2000. — Vol. 36, № 4. — Р. 517–522.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.
54. 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.
55. 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.