Serological level of transforming growth factor-β as a predictive biomarker of aortic enlargement in patients with Marfan syndrome

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Abstract


Marfan syndrome - an inherited, autosomal dominant disease with an expected rate of 3-5/10 000 or fraction of 20-25% of new mutations, accompanied by violation of the connective tissue that occurs as a result of gene mutations FBN1, coding for the synthesis of fibrillin-1, performing the most important role in the modulation physiological bioavailability TGF-β (transforming growth factor-β). Prediction of aortic rupture is based on the identification of risk factors: family history, the absolute size of the aortic root, the rate of expansion of the aorta, which are based on the results of the history and techniques of imaging ultrasound, CT, MRI. At the same time there is a chance of developing aortic rupture under normal aortic root size and the absence of any risk factors, as well as after the prophylactic prosthetic aortic root. This makes it necessary to search for alternative prognostic markers, threatening bundle and rupture of the aorta. Article verified the predictive role of TGF-β as a serological biomarker for assessing the extension of the aortic root in patients with Marfan syndrome (n = 23, F : M / 7 : 16; 33 ± 9.3 years). The article describes the patterns between TGF-β and the size and the reconstruction of the aneurysm of the thoracic aorta. It was found that elevated levels of serum TGF-β1 (49.1 ng/ml Vs 29.15 ng/ml in the control, p < 0.05) in patients with MS diagnosed with an extension of the aortic root (Z > 1.96) can serve as a serological marker to poor prognosis, accompanied by an increase in the size of the aortic root. In patients with normal-sized aorta, and after aortic reconstruction serum TGFβ1 not elevated. Serum TGFβ may be a promising target for therapeutic, diagnostic and prognostic tactics which are not based on imaging techniques.

Andrey S Rudoy

Author for correspondence.
andrewrudoj@gmail.com
Belarusian State Medical University
Russian Federation

MD, PhD, Dr Med Sci, Associate Professor, Head, Department of Military Field Therapy

Alexey M Uryvaev

alexeyuryvaev@gmail.com
Belarusian State Medical University
Russian Federation

Assistant Professor, Department of Military Field Therapy

  • Лунева Е.Б., Малев Э.Г., Рудой А.С., Земцовский Э.В. Тактика ведения пациентов с расширением грудной аорты: выбор методики обследования, оценка результатов // Российский кардиологический журнал. – 2015. – Т. 123. – № 7. – С. 116–119. [Luneva EB, Malev EG, Rudoy AS, Zemtsovskiy EV. Management of the expansion of the thoracic aorta: Select the survey methodology, evaluation results. Rossiyskiy kardiologicheskiy zhurnal. 2015;123(7):116-119. (In Russ.)]
  • Рудой А.С. TGF-beta-зависимый патогенез синдрома Марфана и родственных наследственных нарушений соединительной ткани // Артериальная гипертензия. – 2009. – Т. 15. – № 2. – С. 223–226. [Rudoy AS. TGF-beta-dependent pathogenesis of Marfan syndrome and related inherited disorders of connective tissue. Arterial’naya gipertenziya. 2009;15(2):223-226. (In Russ.)]
  • Рудой А.С. Заболевания верхних отделов желудочно-кишечного тракта у лиц молодого возраста, ассоциированные с наследственными нарушениями соединительной ткани (особенности клинической картины, этиологии, патоморфогенеза и прогноза клинического течения): Автореф. дис. … д-ра мед. наук. – СПб., 2009. [Rudoy AS. Diseases of the upper gastrointestinal tract in young adults associated with hereditary disorders of connective tissue (clinical features, etiology, and prognosis pathomorphogenesis clinical course). [dissertation] Saint Petersburg; 2009. (In Russ.)]
  • Рудой А.С., Урываев А.М., Литвиненко А.М., Денещук Ю.С. Z-критерий как оптимальный параметр оценки эхокардиографических размеров корня аорты в норме и патологии // Медицинский журнал. – 2015. – № 1. – С. 132–139. [Rudoy AS, Uryvaev AM, Litvinenko AM, Deneshchuk YuS. Z-criterion, as the optimal parameter estimation of the echocardiographic aortic root dimensions in health and disease. Meditsinskiy zhurnal. 2015;(1):132-139. (In Russ.)]
  • Cohn RD, Erp CV, Habashi JP, et al. Angiotensin II type 1 receptor blockade attenuates TGF-β-induced failure of muscle regeneration in multiple myopathic states. Nature Medicine Nat Med. 2007;13(2):204-10. doi: 10.1038/nm1536.
  • Devereux RB, Simone GD, Arnett DK, et al. Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age. The American Journal of Cardiology. 2012;110(8):1189-94. doi: 10.1016/ j.amjcard.2012.05.063.
  • Engelfriet P, Mulder B. Is there benefit of β-blocking agents in the treatment of patients with the Marfan syndrome? International Journal of Cardiology. 2007;114(3):300-2. doi: 10.1016/j.ijcard.2006. 01.025.
  • Franken R, Hartog AWD, Waard VD, et al. Circulating transforming growth factor-β as a prognostic biomarker in Marfan syndrome. International Journal of Cardiology. 2013;168(3):2441-6. doi: 10.1016/j.ijcard.2013.03.033.
  • Gleizes P, Munger JS, Nunes I, et al. TGF-β Latency: Biological significance and mechanisms of activation. Stem Cells. 1997;15(3):190-7. doi: 10.1002/stem.150190.
  • Groenink M, Lohuis TAJ, Tijssen JGP, et al. Survival and complication free survival in Marfan’s syndrome: implications of current guidelines. Heart. 1999Jan;82(4):499-504. doi: 10.1136/hrt.82.4.499.
  • Habashi J, Doyle J, Hokm T. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Journal of Vascular Surgery. 2011;54(3):910. doi: 10.1016/j.jvs.2011.07.058.
  • Habashi JP. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006Jul;312(5770):117-21. doi: 10.1126/science.1124287.
  • Holm TM, Habashi JP, Doyle JJ, et al. Noncanonical TGF signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science. 2011;332(6027):358-61. doi: 10.1126/science. 1192149.
  • Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. Journal of Medical Genetics. 2010;47(7):476-85. doi: 10.1136/jmg.2009.072785.
  • Matt P, Schoenhoff F, Habashi J, et al. Circulating transforming growth factor in Marfan syndrome. Circulation. 2009;120(6):526-32. doi: 10.1161/CIRCULATIONAHA.108.841981.
  • Matt P, Habashi J, Carrel T, et al. Recent advances in understanding Marfan syndrome: Should we now treat surgical patients with losartan? The Journal of Thoracic and Cardiovascular Surgery. 2008;135(2):389-94. doi: 10.1016/j.jtcvs.2007.08.047.
  • Neptune ER, Frischmeyer PA, Arking DE, et al. Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome. Nature Genetics Nat Genet. 2003;33(3):407-11. doi: 10.1038/ng1116.
  • Ng CM, Cheng A, Myers LA, et al. TGF-β-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 2004Jan;114(11):1586-92. doi: 10.1172/JCI200422715.
  • Pearson GD, Devereux R, Loeys B, et al. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on Research in Marfan Syndrome and Related Disorders. Circulation. 2008Nov;118(7):785-91. doi: 10.1161/CIRCULATIONAHA.108.783753.

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