Thrombomodulin and Endothelial Dysfunction: A Disease-Modifier Shared between Malignant Hypertension and Atypical Hemolytic Uremic Syndrome.
Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood vessels. Five percent of all patients with atypical hemolytic uremic syndrome (aHUS) have mutations in the gene coding for TM, with a peak presentation in young children. Mutations often translate into quantitative and qualitative abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS is relatively poor with frequent relapses after transplantation despite its membrane-bound character. We observed a woman presenting with malignant hypertension (MHT) and associated kidney, brain, cardiac, and hematological involvement with thrombotic microangiopathy on kidney biopsy. She had a documented mutation of the gene coding for TM, which was associated with both aHUS and an increased risk for venous and arterial thrombosis. As TM has anti-coagulant, anti-inflammatory, and cytoprotective properties and also attenuates alternative complement activation, this glycoprotein could play an active role in other diseases with endothelial involvement apart from aHUS. We discuss the potential role of TM in the pathophysiology of various endotheliopathies including MHT. We also provide a framework for future therapeutic options.
['Demeulenaere|Marieke|M|', 'Devreese|Katrien|K|', 'Vanbelleghem|Hilde|H|', 'De Zaeytijd|Julie|J|', 'Vande Walle|Johan|J|', 'Van Biesen|Wim|W|', 'Van Laecke|Steven|S|']
D000328:Adult D065766:Atypical Hemolytic Uremic Syndrome D002648:Child D002675:Child, Preschool D004730:Endothelium, Vascular D005260:Female D006801:Humans D006974:Hypertension, Malignant D007668:Kidney D018180:Thrombomodulin D057049:Thrombotic Microangiopathies
Thrombomodulin Endothelial Malignant hypertension Thrombotic microangiopathy