Interferon-&ggr; Axis in Graft Arteriosclerosis

  title={Interferon-\&ggr; Axis in Graft Arteriosclerosis},
  author={George Tellides and Jordan S. Pober},
  journal={Circulation Research},
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… 

Interferon-γ-mediated allograft rejection exacerbates cardiovascular disease of hyperlipidemic murine transplant recipients.

This study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.

Interacting mechanisms in the pathogenesis of cardiac allograft vasculopathy.

6 potential contributors to lesion formation are discussed, including conventional risk factors of atherosclerosis; (2) pre- or peritransplant injuries; (3) infection; (4) innate immunity; (5) T-cell-mediated immunity; and (6) B- cell- mediated immunity through production of donor-specific antibody.

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  • R. Mitchell
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    Annual review of pathology
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Because GVD shares many features with more common vascular pathologies, insights gleaned from the understanding of allograft vasculopathy may well impact the treatment for "traditional" atherosclerosis or restenosis lesions.

Immunological and Fibrotic Mechanisms in Cardiac Allograft Vasculopathy.

The data on the immunological and fibrotic processes that are involved in the development of CAV are summarized and areas where a lack of knowledge exists and possible additional research can be completed are pinpointed.

Acute and Chronic Rejection: Compartmentalization and Kinetics Ff Counterbalancing Signals in Cardiac Transplants

  • A. KaulS. Goparaju Iii W M Baldwin
  • Biology, Medicine
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2016
Programmed cell death protein 1 (PD1), a negative costimulator, and its ligand PDL1 were highly upregulated in the interstitium during the resolution of acute rejection, which impacts distinct compartments of cardiac allografts.

Triptolide Attenuates Transplant Vasculopathy Through Multiple Pathways

The role of triptolide is identified in inhibiting TV development and its results provide a basis for developing new treatments to prevent TV-related complications and improve the long-term survival of transplant recipients.

Pathophysiological changes after cardiac transplantation: the role of chronic inflammation and rejection

The paper by Goland et al is unique in tracking endomyocardial biopsy findings, together with an assessment of structure and function of the transplanted heart within the first year, with a clear association between donor-specific anti-HLA antibodies and the development of chronic rejection.

A20-Mediated Modulation of Inflammatory and Immune Responses in Aortic Allografts and Development of Transplant Arteriosclerosis

A20 prevents immune-mediated remodeling of vascular allografts, therefore reduces TA lesions by affecting apoptotic and inflammatory signals and modifying the local cytokine milieu to promote an immunoregulatory response within the vessel wall.

Intimal fibrosis in human cardiac allograft vasculopathy.

AIP1 in graft arteriosclerosis.

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    Trends in cardiovascular medicine
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Allograft-induced proliferation of vascular smooth muscle cells: potential targets for treating transplant vasculopathy.

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  • Biology, Medicine
    Current vascular pharmacology
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The anti proliferative effects that immunosuppressive drugs have on VSMC proliferation are summarized and efforts to define the genes which regulate the vascular response to allograft injury are described, and how some of these proteins may represent targets to reduce VS MC proliferation and attenuate CATV are described.

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A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV, and methods to augment endogenous nitric oxide bioavailability as well as newer immunosuppressive regimens may be protective.

Peripheral expansion of circulating T-helper 1 cells predicts coronary endothelial dysfunction after cardiac transplantation.

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Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts.

Development of GAD, but not parenchymal rejection, requires IFN-gamma; reduced expression of MHC antigens and leukocyte adhesion molecules may contribute to the lack of coronary arteriopathy in hearts allografted into GKO mice.

Human Allograft Arterial Injury Is Ameliorated by Sirolimus and Cyclosporine and Correlates with Suppression of Interferon-&ggr;

SRL plus CsA prevented allograft arteriopathy, correlating with suppression of intragraft interferon-&ggr;, suggesting that SRL effects may result from anti-inflammatory consequences from inhibiting interferons, as well as possible mechanisms of action.

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The reduction in severity and altered composition of vascular thickening in grafts from IFN-gamma -/- recipients shows that IFN -gamma contributes to arteriosclerotic development following transplantation.

Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse hearts: role of interferon-gamma.

A single episode of allogeneic injury mediated by T cells suffices to evoke subsequent graft arteriosclerosis, even in the absence of additional T-cell-mediated injury, and the process appears to depend on IFN-gamma.

Donor-specific cytokine production by graft-infiltrating lymphocytes induces and maintains graft vascular disease in human cardiac allografts.

The results suggest that high levels of Th1 cytokines produced by graft-infiltrating lymphocytes early after transplantation may be responsible for activation of vascular endothelium, leading to the migration and proliferation of smooth muscle cells that is characteristic of GVD.

Pathologic features in long-term cardiac allografts.

The major difference in the two groups was in the pathologic condition of the coronary arteries in the long-term survivors, which more resembled that of naturally occurring atherosclerosis than the characteristic concentric graft coronary disease present in grafts surviving 2 years.

Pathologic features in long-term cardiac allografts.

The major difference in the two groups was in the pathologic condition of the coronary arteries in the long-term survivors, which more resembled that of naturally occurring atherosclerosis than the characteristic concentric graft coronary disease present in grafts surviving 2 years.