Öz
Giriş:
Beta-talasemi majör (BTM), hemolitik anemi ile karakterize otozomal resesif geçişli bir hastalıktır. Sık yapılan eritrosit transfüzyonları sonucu vücutta biriken artmış demir yükü, endotel disfonksiyonuna ve kardiyovasküler komplikasyonlara yol açar. Yüksek asimetrik dimetilar-ginin (ADMA) seviyeleri endotel fonksiyon bozukluğunu gösteren bir belirteçtir. Endocan, birçok organdaki vasküler endotel hücrelerinde sentezlenen çözünür bir proteoglikandır. Yüksek endokan seviyeleri endotelyal disfonksiyonu gösterir. Bu çalışmada BTM hasta grubu ve sağlıklı kontrol grubunda dolaşımdaki ADMA ve endocan düzeylerini değerlendirerek kardiovasküler fonksiyonlar ilişkisini; endotel disfonksiyonu ve kardiyovasküler risk sınıflaması açısından prognostik bir belirteç olup olmadığını belirlemeyi amaçladık.
Gereç ve Yöntem:
Çalışmaya toplam 39 BTM’li hasta ile yaş ve cinsiyet açısından eşleştirilmiş 39 sağlıklı çocuk alındı. Tüm hastaların tıbbi öyküleri kaydedildi ve fizik muayeneleri yapıldı. Tam kan sayımı, retikülosit sayımı, serum ferritin ve demir düzeyi, karaciğer, böbrek fonksiyon testleri, plazma ADMA ve endokan ve proBNP tetkikleri değerlendirildi. Hem hasta hem de kontrol grubundaki tüm çocuklarda pediatrik kardiyolog tarafından kardiyak muayene sonuçları test edildi.
Bulgular:
BTM grubunda ortalama ADMA düzeyi kontrol grubuna göre daha yüksektir. BTM’li hastalarda endocan düzeyleri istatistiksel olarak farklı bulunmadı. Serum endocan ve ADMA seviyeleri kardiyovasküler fonksiyonlarla ilişkisi gösterilemedi.
Sonuç:
BTM hastalarında serum ADMA düzeyleri anlamlı olarak yüksek bulunmasına rağmen, yüksek serum endocan ve ADMA düzeyleri kardiyovasküler fonksiyonlarla ilişkili bulunmamıştır.
Kaynakça
Origa R. β-Thalassemia. Genet Med 2017;19:609-19.
Kwiatkowski JL. Hemoglobinopathies. In: Lanzkowsky P, Lipton JM FJ, (eds). Lanzkowsky’s Manual of Pediatric Hematology and Oncology. 6th ed. Elsevier; 2016: p.188.
Stoyanova E, Trudel M, Felfly H, Lemsaddek W, Garcia D, Cloutier G. Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO. PLoS One 2012;7:38089.
Paul A, Thomson VS, Refat M, Al-Rawahi B, Taher A, Nadar SK. Cardiac involvement in beta-thalassaemia: current treatment strategies. Postgrad Med 2019;131:261-7.
Gursel O, Tapan S, Sertoglu E, Taşçılar E, Eker I, Ileri T, et al. Elevated plasma asymmetric dimethylarginine levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction. Hematology 2018;23:304-308.
Cusmà Piccione M, Piraino B, Zito C, Khandheria BK, Di Bella G, De Gregorio C, et al. Early identification of cardiovascular involvement in patients with β-thalassemia major. Am J Cardiol 2013;112:1246-51.
Frimat M, Boudhabhay I, Roumenina LT. Hemolysis derived products toxicity and endothelium: model of the second hit. Toxins (Basel) 2019;11:660.
Morris C, Gladwin M, Kato G. Nitric oxide and arginine sysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med 2008;8:620-32.
Sandoo A, Veldhuijzen van Zanten JJC., Metsios GS, Carroll D et al. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2015;4:302-12.
Gambardella J, Khondkar W, Morelli MB, Wang X et al. Arginine and endothelial function. Biomedicines. 2020;8:277.
Landim MBP, Casella Filho A, Chagas ACP. Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: Implications for atherogenesis. Clinics 2009;64:471-8.
Böger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality-An update on patient populations with a wide range of cardiovascular risk. Pharmacol Res 2009;60:481-7.
Dogru T, Genc H, Tapan S, Ercin CN, Ors F, Aslan F, et al. Elevated asymmetric dimethylarginine in plasma: An early marker for endothelial dysfunction in non-alcoholic fatty liver disease? Diabetes Res Clin Pract 2012;96:47-52.
Sarrazin S, Adam E, Lyon M, Depontieu, F, Motte V, Landolfi C, et al. Endocan or endothelial cell specific molecule-1 (ESM-1): A potential novel endothelial cell marker and a new target for cancer therapy. Biochim Biophys Acta 2006;1765:25-37.
Balta S, Mikhailidis DP, Demirkol S, Ozturk C, Celik T, Iyisoy A, et al. Endocan: A novel inflammatory indicator in cardiovascular disease? Atherosclerosis 2015;243:339-43.
Delehedde M, Devenyns L, Maurage CA, Vivès RR. Endocan in cancers: A lesson from a circulating dermatan sulfate proteoglycan. Int J Cell Biol 2013;2013:705027.
Cardiac Complications In Thalassaemia Major - Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) - NCBI Bookshelf. Accessed March 11, 2021. https://www.ncbi.nlm.nih.gov/books/NBK269371/
Koohi F, Kazemi T, Miri-Moghaddam E. Ann Hematol 2019;98:1323-31.
Biswas I, Khan GA. Endothelial dysfunction in cardiovascular diseases. Endothel Dysfunct Cardiovasc Dis 2014:291-308.
Haybar H, Shahrabi S, Rezaeeyan H, Shirzad R, Saki N. Endothelial cells: from dysfunction mechanism to pharmacological effect in cardiovascular disease. Cardiovasc Toxicol 2019;19:13-22.
Dowsett L, Higgins E, Alanazi S, Alshuwayer NA, Leiper FC, Leiper J. ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis. J Clin Med 2020;9:3026.
Mohamed ES, Ibrahim B, Amr D, Noha El-K, Mokhtar M. Asymmetric dimethylarginine levels in children with β-thalassemia and their correlations to tricuspid regurgitant jet velocity. Pediatr Blood Cancer 2014;61:1540-3.
Chouliaras GL, Kattamis A, Berdoukas V, Gotsis ED, Mavrogeni S, Ladis V. Cardiac magnetic resonance in transfusion dependent thalassaemia: Assessment of iron load and relationship to left ventricular ejection fraction. Br J Haematol 2010;151:397-401.
Davis BA, O’Sullivan C, Jarritt PH, Porter JB. Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major. Blood 2004;104:263-9.
Unlu M, Karaman M, Ay SA, Balta S, Cakar M, Demirkol S, et al. The comparative effects of valsartan and amlodipine on vascular microinflammation in newly diagnosed hypertensive patients. Clin Exp Hypertens 2013 35(6):418-23.
Kali A, Rathan Shetty KS. Endocan: A novel circulating proteoglycan. Indian J Pharmacol 2014;46:579-83.
Zhao T, Kecheng Y, Zhao X, Hu X, Zhu J, Wang T, et al. The higher serum endocan levels may be a risk factor for the onset of cardiovascular disease: A meta-analysis. Medicine (Baltimore) 2018;97:e13407.
Bessa J, Albino-Teixeira A, Reina-Couto M, Sousa T. Endocan: A novel biomarker for risk stratification, prognosis and therapeutic monitoring in human cardiovascular and renal diseases. Clin Chim Acta 2020;509:310-35.
Aggeli C, Antoniades C, Cosma C, Chrysohoou C, Tousoulis D, Ladis V, et al. Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major. Int J Cardiol 2005;105:80-4.
Menon P, Kocher O, Aird W. Abstract 15455: Endothelial Cell Specific Molecule-1 (ESM-1), a Novel Secreted Proteoglycan Stimulates Vascular Smooth Muscle Cell Proliferation and Migration. Circulation 2011;124:A15455.
Daar S, Al Khabori M, Al Rahbi S, Hassan M, El Tigani A, Pennell DJ. Cardiac T2* MR in patients with thalassemia major: a 10-year long-term follow-up. Ann Hematol 2020;99:2009-17.
Ünsal Ç. Cardiac Functions and Indicators Of Endothelial Activation in Patients With Β-Thalassemia Major. Adana; 2005.
