Circulating Thrombomodulin as a Molecular Marker of Endothelium Damage in Renal Transplant Recipients

Dr. İbrahim C. Haznedaroğlu, 36. sok. Sun apt. No: 3/2, 06490, Bahçelievler, TR-06490 Ankara (Turkey) Dear Sir, Thrombomodulin (TM) is a cell surface glycoprotein located at the luminal surface of vascular endothelium as a membrane-bound high-affinity thrombin receptor [1], It inactivates thrombin and stimulates anticoagula-tory pathways. TM therefore belong to the anticoagulant defence system against thrombosis and plays a crucial role in the regulation of blood coagulation and fibrinolysis in vivo [2]. Consequently, quantitative and/or qualitative impairment of TM could possibly play a pathogenetic role in the thrombo-genesis and endothelial damage [3]. A smaller soluble form of TM has been isolated from human blood and urine [4]. The structure of soluble TM is not known but is thought to be similar to the soluble protein obtained after proteolytic modification of TM with elastase [5], a cleaved form of tissue TM with loss of part of the trans-membrane domain and the cytoplasmatic tail [6]. Therefore soluble TM, which exists in circulating plasma as heterogenous fragments, appears to be derived from injured endothelial cells or to be proteolytically cleaved from TM by proteases [7]. Soluble TM is cleared from the circulation by the kidneys and liver [2]. The study was a cross-sectional determination of TM, a major component on the endothelial surface, concentrations in plasma from renal transplant recipients and healthy volunteers. Seventeen renal transplant recipients with normal graft function (serum creatinine < 2 mg/dl; 8 females, 9 males, age 31 ± 2 years, mean transplantation duration 34 ± 6 months), 7 renal transplant recipients in chronic rejection (serum creatinine > 2 mg/dl; 2 females, 5 males, age 39 ± 3 years, mean transplantation duration 44 ± 11 months) and 15 nonsmoking healthy volunteers (7 females, 8 males, age 26 ± 9 years) with normal renal function were included in the study. Patients selected for this study were on triple