PROGRESS IN UREMIC TOXIN RESEARCH: Endothelium and Vascular Smooth Muscle Cells in the Context of Uremia

Abstract

It is obvious that retention of uremic toxins leads to endothelial dysfunction, which in turn initiates proliferation of vascular smooth muscle cells. Yet, the entity of the cascade of pathomechanisms has not sufficiently been elucidated. Endothelial dysfunction inevitably and irreversibly leads to progressive cardiovascular dysfunction and thereby represents the beginning of a life-limiting cascade. This review highlights important findings in this field.

Potential Beneficial Effects of<i> Tulbaghia violacea</i> William Henry Harvey (Alliaceae) on Cardiovascular System - A Review

“…The VSMCs are the major cellular component of the vascular media and mediate vasodilatation and vasoconstriction; and are innervated by both sympathetic and parasympathetic fibres [42]. The autonomic nervous system (ANS) consists of both the sympathetic and parasympathetic nervous systems, the activities of both systems are normally in dynamic balance, and plays a vital role in the control of cardiovascular activity [43].…”

Cardiovascular Biomarkers in Chronic Kidney Disease

“…It has been shown in numerous studies to be an independent risk factor for clinical atherosclerosis. Furthermore, plasma leptin correlates with some markers of subclinical atherosclerosis in renal failure patients (11,12,18). Its increase in CKD is due not only to a decreased glomerular filtration rate, but also to decreased catabolism in renal parenchymal cells and increased synthesis influenced by immunological and metabolic factors, primarily insulin and tumor necrosis factor-a (TNF-a) (19).…”

“…Elevated levels of dicarbonyl glycating agents in patients on dialysis, the so-called dicarbonyl stress, result from the changes in their endogenous production, alterations in the activity of enzymes involved in anti-glycation defense and their decreased clearance (13). Endothelial dysfunction, increased atherogenicity of LDL and proinflammatory activity of AGEs may associate protein glycation with an increased risk of CVD in ESRD patients (8,13) Asymmetric dimethylarginine (ADMA), a free water-soluble low molecular weight solute and a catabolite of proteins containing methylated arginine residue, causes endothelial dysfunction by direct and indirect effects on NO activity, and is now considered a strong marker of atherosclerosis and a predictor of mortality and CVD complications in CKD and ESRD (11). Increased ADMA in uremia may be induced by increased enzymatic synthesis or reduced enzymatic degradation (15).…”

“…In addition, many other uremic toxins such as uric acid, dinuclueoside polyphosphates, b2-micro globulin, interleukin-18 (IL-18), IL-1b, TNF-a and angiotensin-II have been implicated in the devel opment of endothelial dysfunction and initiation and progression of atherosclerosis as a chronic inflammation con dition, primarily by acting proinflammatory and increasing oxidative stress (8,11). Proinflammatory cytokines basically represent secondary uremic toxins, since their expression is initially triggered by the uremic condition and the retention occurs due to loss of renal clearance.…”

“…The vascular toxins include indox yl sulphate, which acts mainly via pro-oxidant mechanisms (11) and is possibly involved in vascular remodeling (12).…”