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Circulating thrombomodulin in ischemic heart disease: correlation with the extent and severity of coronary atherosclerosis
Critical Care volume 8, Article number: P106 (2004)
Abnormal endothelial physiology has been implicated both in early atherogenesis and, later, in the control of dynamic plaque behavior. The biologic link between endothelial damage and atherosclerosis may be related to decreased arterial bioavailability of nitric oxide (NO), which may predispose to leucocyte and platelet adhesion, vasoconstriction and smooth muscle cell proliferation. Substances released by the endothelium include prostacyclin, NO, endothelin, von Willebrand factor and thrombomodulin (TM), and so on.
TM is an integral membrane glycoprotein that can change the function of thrombin, to an anticoagulant through activation of protein C – which, in the presence of protein S, inactivates factor VIIIa and factor Va, and thereby inhibits further formation of thrombin.
Soluble TM is thought to indicate endothelial-cell damage. A positive relation between the concentration of soluble thrombomodulin and the risk of atherosclerotic disease is widely assumed.
Aim of the study
To assess the diagnostic role of circulating TM as a marker of the extent and severity of coronary arterial atherosclerosis. We studied 150 patients with ischemic heart disease (118 male, 32 female; mean age 53.4 ± 8.3 years, ranging from 32 to 80 years), together with 20 nonischemic patients who were catheterized prior to valve replacement (13 male, seven female; mean age 58.4 ± 4.5 years) serving as controls. Of the 150 ischemic patients, 77 had anginal pain (AP) and 73 had acute myocardial infarction (AMI).
Following clinical evaluation, all patients were subjected to 12-lead ECG and routine laboratory work, and coronary arteriography to assess the extent and severity of the stenotic lesions using the Gensini scoring system. All patients had TM levels, measured in arterial samples withdrawn from the coronary artery during the catheter procedure using the enzyme immunoassay ELISA.
Compared with the control subjects, the ischemic patients exhibited significantly higher levels of serum TM (42.5 ± 15.4 vs 2.8 ± 0.8, P < 0.0000), with progressively higher levels of serum TM from the anginal group to the AMI group (35.7 ± 11.3 vs 49.6 ± 16.1, P < 0.000001).
Serum TM correlated significantly with the severity of coronary artery pathology, expressed as the Gensini score with P < 0.000 for the angina group and P < 0.000 for the AMI group. Again, both groups exhibited significant correlation between serum TM and the number of diseased vessels, with P < 0.000 for both groups.
TM, an endothelial glycoprotein resulting from the damage to the vascular endothelium by the atheromatous process, showed significant correlation with the extent and severity of coronary artery disease (expressed by the Gensini score system). The higher TM level in the AMI group compared with the AP group points to the more significant endothelial damage in the former compared with the latter. That stresses the importance of serum TM as a molecular marker of endothelial dysfunction in acute ischemic syndromes.
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Rizk, A., Samir, N., El Naggar, A. et al. Circulating thrombomodulin in ischemic heart disease: correlation with the extent and severity of coronary atherosclerosis. Crit Care 8, P106 (2004). https://doi.org/10.1186/cc2573
- Acute Myocardial Infarction
- Gensini Score
- Anginal Pain
- Ischemic Patient
- Acute Myocardial Infarction Group