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Received Dec 24, 2017; Revised Apr 16, 2018; Accepted May 10, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Chronic kidney disease (CKD) patients are more likely to develop cardiovascular disease (CVD) than age-matched counterparts in the general population. As a consequence, the risk of death in CKD patients due to cardiovascular disease is much higher than the risk of requiring dialysis [1, 2].
Chronic inflammation is directly related to several complications of CKD, including accelerated atherosclerosis and left ventricular hypertrophy [2, 3]. Chronic low-grade inflammation is common in patients with coexisting CKD and CVD and plays a pivotal role in the development of atherosclerotic plaques by driving oxidative stress and stimulating production of inflammatory cytokines leading to activation of chemokines and adhesion molecules [3–5].
Endotoxin (lipopolysaccharide), a glycolipid that comprises most of the outer wall of gram-negative bacteria, is a potential source of inflammation in CKD patients [6, 7]. It is reported that circulating endotoxaemia constitutes a strong risk factor for atherosclerotic CVD [8–10]. This finding suggests that chronic exposure to endotoxins may be related to subclinical atherosclerosis and represents a reversible CVD risk factor in CKD patients.
Atherosclerosis is a complex disease process in which inflammation plays a central role in various pathogenetic mechanisms that contribute to the progressive structural changes that are characteristic of atherogenesis [11, 12]. Besides promoting atherosclerosis, inflammation also plays a significant role in the process of plaque rupture and arterial thrombosis, leading to vascular occlusion and infarction [13]. Thus, inflammation has been found to be a significant predictor of cardiovascular mortality in CKD patients [14].
Transforming growth factor-β (TGF-β), a multifunctional inflammatory cytokine, is produced by many inflammatory cells including leucocytes, macrophages, smooth muscle cells, and platelets [15–18]. There are three isoforms of TGF-β: TGF-β1, TGF-β2, and TGF-β3. Transforming growth factor-β1, the most extensively studied of these three isoforms, exhibits anti-inflammatory and antiproliferative properties by inhibiting the synthesis of tumour necrosis factor-α (TNF-α) or by downregulating the proinflammatory effects of IL-1β and interferon-γ [19,...