Overexpression of Activated Nuclear Factor‐κ B in Aorta of Patients With Coronary Atherosclerosis

Zhang, Wei; Xing, Shan; Sun, Xue; Xing, Quansheng

doi:10.1002/clc.20482

Cited by 18 publications

(14 citation statements)

References 23 publications

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“…CD40/CD40L signalling occurs via activation of NF-κB (Nuclear Factor-κB) which activates many of the genes involved in the inflammatory response that are pivotal in the pathogenesis of vascular injury [ 2 ]. Consequently, activated NF-κB has been detected in a rabbit model of ASVD [ 3 ] and in human ASVD but not in normal vessels [ 4 ]. Furthermore, activation of NF-κB has been also involved in the progression of renal tubulointerstitial lesions in experimental proteinuric nephropathies and in the development of human glomerulonephritis [ 5 ], a possible link between CKD and ASVD.…”

Section: Resultsmentioning

confidence: 99%

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study

et al. 2015

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BackgroundChronic Kidney Disease (CKD) and inflammation are risk factors for atherosclerotic vascular disease (ASVD). In inflammatory conditions, Nuclear Factor-κB (NF-κB) is frequently activated and it has been detected in human ASVD. In this work, we investigated if the degree of inflammation and of NF-κB activation were increased in the aorta of patients with CKD.MethodsThis is a case–control pilot study performed on 30 abdominal aorta samples from 10 human autopsies. Cases were patients with CKD and controls patients with normal glomerular filtration rate (eGFR). Infiltrating mononuclear cells (S100+, CD3+, CD40+, CD40L+) and activation of NF-κB were identified by immunohistochemistry.FindingsThe number of cells in the intima which showed activated nuclear NF-κB correlated with severity of ASVD lesions (r = 0.56, p = 0.003), with numbers of CD3+ lymphocytes in adventitia (r = 0.50, p = 0.008), with numbers of CD40+ cells in the intima (r = 0.59, p = 0.002) or in the adventitia (r = 0.45, p = 0.02), and with numbers of CD40L+ cells in the intima (r = 0.51, p = 0.011). Increased numbers of S100+ Intimal Dendritic cells (IDCs) were associated with ASVD (p = 0.03) and CKD (p = 0.01).ConclusionsNumber of CD3+ cells, of CD40+ cells, of CD40L+ cells and the degree of NF-κB activation were increased in ASVD lesions suggesting a role for the adaptive T cell in the development of ASVD lesions. IDCs were associated both with ASVD and CKD suggesting a role of these cells in the pathogenesis of ASVD in CKD.

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Section: Resultsmentioning

confidence: 99%

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study

et al. 2015

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“…In the present study, the specimens were whole arterial walls, consisting of tunica intima, media and externa. These arterial tissues were used for the investigation of the expression levels of certain inflammatory factors, including nuclear factor-κB, Toll-like receptor 4 and high-mobility group protein B1, in atherosclerotic patients ( 33 – 35 ). Given the fact that aortic tissues were not available from healthy subjects, renal artery tissues from kidney transplant cases were instead used as a control.…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular cell adhesion molecule-1 in the aortic tissues of atherosclerotic patients and the associated clinical implications

Chen

Gong

et al. 2015

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the expression level of vascular cell adhesion molecule-1 (VCAM-1) in the aortic tissues of atherosclerotic patients and to explore the associated clinical implications. Full-thickness aortic wall tissue samples were collected from atherosclerotic patients. Biochemical analysis was used for the detection of the serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) [Lp (a)], apolipoprotein (Apo) AI and Apo-B. Coronary angiography and SYNTAX scoring were used to determine the extent and severity of the disease. Immunohistochemistry was employed for the detection of the VCAM-1 protein expression levels in the arterial tissues. Significant differences were observed in the blood lipid levels between atherosclerotic patients and control subjects. Immunohistochemistry indicated that the aortic VCAM-1 expression level in atherosclerotic patients was 0.23±0.06 optical density (OD) units, which was significantly higher than that in the control subjects (0.08±0.03 OD units). In the atherosclerotic patients, the aortic VCAM-1 expression was positively correlated with the serum levels of TG (r=0.347), TC (r=0.469), LDL-C (r=0.463), Lp (a) (r=0.507) and Apo-B (r=0.384), while VCAM-1 and HDL-C were negatively correlated (r=-0.319). Furthermore, a higher SYNTAX score was accompanied by a higher VCAM-1 expression level (r=0.532), and an elevated aortic VCAM-1 expression was associated with certain cardiovascular risk factors. In conclusion, aortic VCAM-1 expression is associated with the severity of atherosclerosis and cardiovascular risk factors, indicating that VCAM-1 plays a role in the pathogenesis of atherosclerosis.

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“…NF-κB has been associated with pro-inflammatory responses in atherosclerosis (Monaco et al 2004;Zhang et al 2009); however, emerging in vivo data suggests that NF-κB also regulates anti-inflammatory processes in the atherosclerotic plaque (Xanthoulea et al 2005). For example, in a study of atherosclerosis-prone low-density lipoprotein receptor knock-out (LDLR −/− ) mice with a macrophagerestricted deletion of IKK2, the mice developed more severe atherosclerosis and had markedly decreased levels of the anti-inflammatory cytokine, IL-10 ( Kanters et al 2003).…”

Section: Samira Salari and Tara Seibert Contributed Equally To This Workmentioning

confidence: 99%

Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages

Salari

Seibert

Chen

et al. 2013

Cell Stress and Chaperones

114

134

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Heat shock protein 27 (HSP27) shows attenuated expression in human coronary arteries as the extent of atherosclerosis progresses. In mice, overexpression of HSP27 reduces atherogenesis, yet the precise mechanism (s) are incompletely understood. Inflammation plays a central role in atherogenesis, and of particular interest is the balance of pro-and anti-inflammatory factors produced by macrophages. As nuclear factor-kappa B (NF-κB) is a key immune signaling modulator in atherogenesis, and macrophages are known to secrete HSP27, we sought to determine if recombinant HSP27 (rHSP27) alters NF-κB signaling in macrophages. Treatment of THP-1 macrophages with rHSP27 resulted in the degradation of an inhibitor of NF-κB, IκBα, nuclear translocation of the NF-κB p65 subunit, and increased NF-κB transcriptional activity. Treatment of THP-1 macrophages with rHSP27 yielded increased expression of a variety of genes, including the pro-inflammatory factors, IL-1β, and TNF-α. However, rHSP27 also increased the expression of the anti-inflammatory factors IL-10 and GM-CSF both at the mRNA and protein levels. Our study suggests that in macrophages, activation of NF-κB signaling by rHSP27 is associated with upregulated expression and secretion of key pro-and anti-inflammatory cytokines. Moreover, we surmise that it is the balance in expression of these mediators and antagonists of inflammation, and hence atherogenesis, that yields a favorable net effect of HSP27 on the vessel wall.

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Overexpression of Activated Nuclear Factor‐κ B in Aorta of Patients With Coronary Atherosclerosis

Cited by 18 publications

References 23 publications

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study

Expression of vascular cell adhesion molecule-1 in the aortic tissues of atherosclerotic patients and the associated clinical implications

Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages

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