Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

Booth, A. D.; Jayne, D.; Kharbanda, Rajesh K.; McEniery, CM; Mackenzie, Iain; Brown, Jerry M.; Wilkinson, I.B.

doi:10.1097/00004872-200406002-00025

Cited by 23 publications

(32 citation statements)

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“…TNF has a key role in autoimmune and inflammatory disorders including vasculitis , in part via stimulating endothelial cell inflammation and leukocyte–endothelial cell interactions. The current study reveals a novel, previously unrecognized function of endothelial XBP‐1 in TNF‐induced vasculitis.…”

Section: Discussionmentioning

confidence: 99%

Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis

Ziogas

Muders

Economopoulou

et al. 2015

Arthritis & Rheumatology

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Objective Endothelial cell activation by tumor necrosis factor (TNF) and associated leukocyte infiltration are hallmarks of vasculitis. The aim of this study was to investigate the potential role of the cellular stress–associated endothelial X‐box binding protein 1 (XBP‐1) transcription factor in TNF‐induced endothelial cell inflammation and vasculitis. Methods Mice with an endothelial cell–specific XBP‐1 deficiency were used in a modified local Shwartzman reaction (LSR) model of TNF‐induced small vessel vasculitis. To address the contribution of XBP‐1 to the TNF‐mediated inflammatory response in endothelial cells, we examined the activation of XBP‐1 expression by TNF as well as the effect of XBP‐1 knockdown in endothelial cells on TNF‐induced signaling, proinflammatory gene expression, and leukocyte–endothelial cell adhesion. Results The active spliced form of XBP‐1 in endothelial cells was triggered by TNF. In addition, endothelial XBP‐1 contributed to the sustained TNF‐triggered NF‐κB−dependent transcriptional activation of proinflammatory molecules, which was associated with leukocyte–endothelial cell adhesion. In the LSR model, endothelial cell–specific XBP‐1–deficient mice displayed significantly less vascular damage, accompanied by reduced perivascular neutrophil infiltration, as compared with wild‐type mice. Conclusion Endothelial XBP‐1 is activated by TNF and regulates leukocyte–endothelial cell adhesion in vitro as well as neutrophil infiltration and vascular damage in murine vasculitis.

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Section: Discussionmentioning

confidence: 99%

Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis

Ziogas

Muders

Economopoulou

et al. 2015

Arthritis & Rheumatology

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“…As part of clinical research paradigms, vascular inflammation models are employed as a method to examine vascular reactivity in preexisting systemic inflammation. Patients with small vessel vasculitis had increased levels of inflammatory cytokines as well as greater levels of arterial stiffness as compared to age-matched healthy control subjects (Booth et al, 2004). Arterial stiffness, recognized as a risk factor for CMVD, appears directly correlated to levels of systemic inflammation and is reduced by anti-inflammatory treatments (Booth et al, 2004).…”

Section: Vascular-induced Behavioral Disruption: In the Labmentioning

confidence: 99%

“…Patients with small vessel vasculitis had increased levels of inflammatory cytokines as well as greater levels of arterial stiffness as compared to age-matched healthy control subjects (Booth et al, 2004). Arterial stiffness, recognized as a risk factor for CMVD, appears directly correlated to levels of systemic inflammation and is reduced by anti-inflammatory treatments (Booth et al, 2004). Taken together, both rodent and clinical models support the direct involvement of inflammatory mediators in the reactivity and tone of central and peripheral vasculature.…”

Section: Vascular-induced Behavioral Disruption: In the Labmentioning

confidence: 99%

Heartsick: psychiatric and inflammatory implications of cerebromicrovascular disease

Nemeth

Haroon

Neigh

2013

Int J Geriat Psychiatry

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Although the concept of cerebrovascular-induced behavioral change has existed for over 100 years, the difficulty of diagnosis, the slow progression of CMVD, and the lack of causative data have led to an underestimation of the patient population and poor treatment strategies. Preclinical studies have focused on the use of microsphere embolic models and vascular inflammation models to assess the mechanisms of, and treatment options for, CMVD. Though preclinical models provide support for correlative data collected in the clinic, translational reciprocity has not been established. The lack of clinical appreciation for the role of cerebrovascular health in brain function may result in missed diagnoses and inadequate treatment of underlying cardiovascular disease. Enhanced recognition of symptoms and disease presentation will allow for earlier prevention, detection, and identification of novel targets for drug development and other intervention strategies.

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“…Indeed, EC dysfunction is described in CVD, 16 as well as in systemic autoimmune diseases. [17][18][19][20][21][22] EC dysfunction can be measured by different methods. The most commonly used is flow-mediated dilation, but increasingly, laser Doppler fluxmetry in combination with iontophoresis is used.…”

Section: Systemic Autoimmune Diseases Such As Systemic Lupus Erythemamentioning

confidence: 99%

“…30,31 Note that EC dysfunction in systemic vasculitis is related to inflammation, as reflected by CRP levels and the Birmingham Vasculitis Activity Score. 18,19,32 Furthermore, heat shock proteins (HSPs) have been suggested to contribute to the cascade that leads to atherosclerosis. It has been demonstrated that classic atherosclerosis risk factors, such as high blood pressure, smoking, diabetes, and chemically altered lipoproteins, act as stress factors for ECs, which express HSPs upon activation.…”

Section: Autoantibodiesmentioning

confidence: 99%

Accelerated Atherosclerosis in Patients with Systemic Autoimmune Diseases

Leeuw

Kallenberg

Bijl

2005

Annals of the New York Academy of Sciences

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Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis, the major underlying cause of CVD. In patients with systemic autoimmune diseases, it has been shown that traditional risk factors for CVD cannot completely explain the prevalence of atherosclerosis. Therefore, in addition to these traditional factors, nontraditional risk factors are suggested to contribute to atherogenesis. All risk factors, traditional and nontraditional, contribute to endothelial activation that, followed by endothelial dysfunction, is seen as one of the first steps in this process. This review updates information on the factors that contribute to accelerated atherosclerosis in patients with systemic autoimmune diseases, such as disease-related factors, inflammatory mediators, and advanced glycation end products.

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Infliximab Improves Endothelial Dysfunction in Systemic Vasculitis

Cited by 23 publications

References 0 publications

Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis

Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis

Heartsick: psychiatric and inflammatory implications of cerebromicrovascular disease

Accelerated Atherosclerosis in Patients with Systemic Autoimmune Diseases

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