Elevated Serum Levels of the CXCR3 Chemokine ITAC Are Associated With the Development of Transplant Coronary Artery Disease

Kao, John; Kobashigawa, Jon A.; Fishbein, Michael C.; MacLellan, W. Robb; Burdick, Marie D.; Belperio, John A.; Strieter, Robert M.

doi:10.1161/01.cir.0000069270.16498.75

Cited by 56 publications

(41 citation statements)

References 19 publications

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“…69 The relevant ECs may be those that line the arterial lumen or those that line microvessels of the adventitia. A pathway of selective recruitment, judged by selective CXCR3-binding chemokine expression, does appear to operate in human GA, [23][24][25][26][27] as well as in our human artery GA model. 38 These studies have demonstrated that CXCR3 and CCR5 ligands are synthesized in both the parenchymal and vascular compartments of human cardiac allografts.…”

Section: T H 1 Effector Cells and Cd8mentioning

confidence: 85%

“…Notably, an increased expression of the IFN-␥-inducible chemokines RANTES (CCL5) and I-TAC and an increased expression of the T H 1-associated chemokine receptor CXCR3 have been described in arteriosclerotic coronary arteries. 25,26 The most convincing evidence for an association of IFN-␥ with GA was a recent detailed inventory of infiltrating leukocytes and cytokines in arteriosclerotic coronary arteries. van Loosdregt et al found that the expression of IFN-␥, IFN-␥-inducible chemokines (Mig, IP-10, ITAC, RANTES, and fractalkine/CX3CL1), and markers of IFN-␥-secreting T H 1 cells (CXCR3, CCR5, and CX3CR1) were increased in epicardial coronary arteries from transplanted hearts with documented GA compared with referent specimens.…”

Section: Evidence For a Pathogenetic Role Of Ifn-␥ In Gamentioning

confidence: 99%

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Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

107

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Abstract-Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-␥, is a key effector in graft arteriosclerosis, which, together with the IFN-␥-inducing cytokine interleukin-12 and IFN-␥-inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN-␥ axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN-␥ production within the artery wall, the effects of IFN-␥ on vessel wall cells, and the outcome of therapeutic agents on IFN-␥ production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN-␥ synthesis or actions. (Circ Res. 2007;100:622-632.)

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Section: T H 1 Effector Cells and Cd8mentioning

confidence: 85%

Section: Evidence For a Pathogenetic Role Of Ifn-␥ In Gamentioning

confidence: 99%

Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

107

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“…It was demonstrated that patients with mild to moderate hypertension without coronary artery disease (CAD) have elevated serum levels of inflammatorymediators such as the C-C chemokines CCL2. As far as C-X-C chemokines are concerned, there is only one previous experience demonstrating a correlation between serum IFN-inducible T-cell a chemoattractant (I-TAC or CXCLll) levels and development of transplant CAD in humans (12).…”

mentioning

confidence: 99%

High Serum Levels of CXC (CXCL10) and CC (CCL2) Chemokines in Untreated Essential Hypertension

Antonelli

Fallahi

Ferrari

et al. 2012

Int J Immunopathol Pharmacol

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Hypertension has been suggested to exert pro-inflammatory actions through increased expression of several mediators, including chemokines. Chemokines are involved in inflammatory and autoimmune disorders, and in the formation of atherosclerotic lesions through promotion of inflammatory cell migration. The aim of this study is to evaluate the influence of high blood pressure on circulating levels ofthe prototype chemokines C-X-C motifligand (CXCL)10 and C-C motifligand (CCL)2 in 140 patients with essential hypertension not affected by thyroid disorders or overt autoimmune or inflammatory diseases, and 140 gender-and age-matched healthy controls. Mean CXCLI0 and CCL2 levels were significantly higher in hypertensive patients than in controls. Among hypertensive patients, chemokines levels were higher in those with systo-diastolic hypertension compared to those with isolated systolic hypertension. In a multiple linear regression model using CXCLI0 or CCL2 as dependent variables and age, body mass index, glycemia, serum creatinine, high-density-lipoprotein (HDL) and low-densitylipoprotein (LDL) cholesterol, triglycerides, and systolic or diastolic blood pressure values as covariates, only systolic or diastolic blood pressure values were significantly related to CXCLI0 or CCL2levels. In conclusion, this study demonstrates increased circulating levels of the prototype chemokines CXCLI0 and CCL2 in patients with hypertension.

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“…10,11 These chemokines and others such as RANTES (regulated on activation normal T cell expressed and secreted) and fractalkine are directly linked with CAV development in animal studies. [12][13][14] Studies for the role of chemokines in human CAV development are limited to 2 immunohistochemical investigations 15,16 and studies on human coronary arteries transplanted in severe combined immunodeficiency mice reconstituted with human peripheral blood mononuclear cells (PBMCs). 17,18 CAV develops in rodents as early as 14 days after transplantation, 12 but its course in humans is relatively slow.…”

mentioning

confidence: 99%

The Chemokine and Chemokine Receptor Profile of Infiltrating Cells in the Wall of Arteries With Cardiac Allograft Vasculopathy Is Indicative of a Memory T–Helper 1 Response

et al. 2006

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Background-Despite improvement in short-term patient survival after heart transplantation (HTx), long-term survival rates have not improved much, mainly because of cardiac allograft vasculopathy (CAV). Cytokines and chemokines are considered to play an important role in CAV development. Interleukin-4 and interleukin-10 were expressed at the same level in both HTx groups and references. In HTxϩCAV, all CϩCR, but especially the T-helper 1 (TH1) CϩCR, were more abundant than in the HTxϪCAV and references. However, TH2 CCR4 expression did not differ significantly between both HTx groups. Conclusions-In coronary arteries with CAV, most T cells are CD4 ϩ and express human leukocyte antigen DR. These activated TH cells are mainly memory TH1 cells on the basis of their CϩCR profile and cytokine expression. Methods and Results-We

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Elevated Serum Levels of the CXCR3 Chemokine ITAC Are Associated With the Development of Transplant Coronary Artery Disease

Abstract: Background-Human

Cited by 56 publications

References 19 publications

Interferon-γ Axis in Graft Arteriosclerosis

Interferon-γ Axis in Graft Arteriosclerosis

High Serum Levels of CXC (CXCL10) and CC (CCL2) Chemokines in Untreated Essential Hypertension

The Chemokine and Chemokine Receptor Profile of Infiltrating Cells in the Wall of Arteries With Cardiac Allograft Vasculopathy Is Indicative of a Memory T–Helper 1 Response

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