Does Uremia Cause Vascular Dysfunction?

Vascular dysfunction induced by uremia has 4 main aspects. (1) Atherosclerosis is increased. Intima-media thickness is increased, and animal studies have established that uremia accelerates atherosclerosis. Uremic toxins are involved in several steps of atherosclerosis. Leukocyte activation is stimulated by guanidines, advanced glycation end products (AGE), p-cresyl sulfate, platelet diadenosine polyphosphates, and indoxyl sulfate. Endothelial adhesion molecules are stimulated by indoxyl sulfate. Migration and proliferation of vascular smooth muscle cells (VSMC) are stimulated by local inflammation which could be triggered by indoxyl sulfate and AGE. Uremia is associated with an increase in von Willebrand factor, thrombomodulin, plasminogen activator inhibitor 1, and matrix metalloproteinases. These factors contribute to thrombosis and plaque destabilization. There is also a decrease in nitric oxide (NO) availability, due to asymmetric dimethylarginine (ADMA), AGE, and oxidative stress. Moreover, circulating endothelial microparticles (EMP) are increased in uremia, and inhibit the NO pathway. EMP are Published online: June 21, 2011 P. Brunet Centre de Néphrologie et de Transplantation Rénale, Hôpital de la Conception 147, Bd Baille FR–13005 Marseille (France) Tel. +33 4 91 38 23 06, E-Mail philippe.brunet @ ap-hm.fr © 2011 S. Karger AG, Basel 1420–4096/11/0344–0284$38.00/0 Accessible online at: www.karger.com/kbr D ow nl oa de d by : 54 .7 0. 40 .1 1 1/ 9/ 20 18 3 :2 2: 20 A M