INTRODUCTION
BTM is an autosomal recessive disease characterized by hemolytic anemia in which one or more of the hemoglobin beta chain is produced defective.1 Regular erythrocyte transfusion is required to prevent clinical complications due to low hemoglobin levels.2 However, increased iron load accumulated in the body as a result of frequent erythrocyte transfusions leads to many organ damage, including endothelial dysfunction and cardiovascular complications.3,4 Peroxidative damage due to iron load caused by repeated blood transfusions and possible coronary artery diseases are thought to be responsible for the pathogenesis.5,6 Vascular and cardiac complications are based on endothelial dysfunction and altered carotid artery structure, which are present in the nature of thalassemia.3
It has been shown in many studies in the literature that the arginine-nitric oxide pathway triggered by hemolysis causes endothelial function7,8. NO is a mediator that controls vascular tone by vasodilation, causes thrombocyte dysfunction, prevents the adhesion of leukocytes, and reduces vascular intimal cell production.9 NO is synthesized from the endothelium by converting L-arginine to L-citrulline by endothelial NO synthase (eNOS), whose activity is dependent on nicotinamide adenine dinucleotide phosphate. 10 The addition of two methyl radicals to arginine by the action of methyltransferase nuclear proteins leads to the production of ADMA, which competes with L-arginine and reduces NO formation in the vascular wall.11 High ADMA levels inhibit NO synthesis. Thus, it disrupts the endothelial function and supports atherosclerosis. ADMA has been recognized as an early marker for endothelial dysfunction and also as an independent factor for future cardiovascular disease.12,13
Endocan (formerly known as endothelial cell specific molecule-1, ESM-1) is a 50 kDa soluble proteoglycan that can be detected in circulation and is synthesized in vascular endothelial cells in many organs.14 It shows its effect by regulating the adhesion rate of cells to the vascular wall. High levels of endocan indicate endothelial dysfunction.15 Apart from that, it plays a role in cell migration, adhesion, proliferation and neovascularization, which are biologically indispensable.16
Considering this information, in our study, it was aimed to determine whether there is a correlation with cardiac evaluation instruments by evaluating circulating ADMA and endocan levels in transfusion-dependent BTM patient group and healthy control group and whether they can be a prognostic marker in terms of endothelial dysfunction and cardiovascular risk stratification.