Endothelial injury: cause and effect of alloimmune inflammation

Vos, I.H.C.; Briscoe, David M.

doi:10.1034/j.1399-3062.2002.t01-1-02002.x

Cited by 23 publications

(18 citation statements)

References 135 publications

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“…33,34 A variety of studies have evaluated the possible beneficial effects of new or modified organ preservation solutions on liver function and viability upon reperfusion 28,35 ; however, none of them focused at improving endothelial protection during cold storage. In our study, we addressed this question by analyzing the possible beneficial effects of adding simvastatin, a drug known for it vasoprotective properties, to a standard solution for organ preservation.…”

Section: Discussionmentioning

confidence: 99%

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

et al. 2012

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Pathophysiological alterations in the endothelial phenotype result in endothelial dysfunction. Flow cessation, occurring during organ procurement for transplantation, triggers the endothelial dysfunction characteristic of ischemia/reperfusion injury, partly due to a reduction in the expression of the vasoprotective transcription factor Kruppel-like Factor 2 (KLF2). We aimed at (1) characterizing the effects of flow cessation and cold storage on hepatic endothelial phenotype, and (2) ascertaining if the consequences of cold stasis on the hepatic endothelium can be pharmacologically modulated, improving liver graft function. Expression of KLF2 and its vasoprotective programs was determined in (i) hepatic endothelial cells (HEC) incubated under cold storage conditions with or without the KLF2-inducer simvastatin, and (ii) rat livers not cold stored or preserved in cold University of Wisconsin solution (UWS) supplemented with simvastatin or its vehicle. In addition, upon warm reperfusion hepatic vascular resistance, endothelial function, nitric oxide vasodilator pathway, apoptosis, inflammation, and liver injury were evaluated in not cold stored livers or livers preserved in cold UWS supplemented with simvastatin or vehicle. Expression of KLF2 and its vasoprotective programs decrease in HEC incubated under cold storage conditions. Cold-stored rat livers exhibit a time-dependent decrease in KLF2 and its target genes, liver injury, increased hepatic vascular resistance, and endothelial dysfunction. The addition of simvastatin to the storage solution, maintained KLF2-dependent vasoprotective programs, prevented liver damage, inflammation, and oxidative stress and improved endothelial dysfunction. Conclusion: Our results provide a rationale to evaluate the beneficial effects of a vasoprotective preservation solution on human liver procurement for transplantation. (HEPATOLOGY 2012;55:921-930)

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Section: Discussionmentioning

confidence: 99%

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

et al. 2012

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“…Leukocytes damaging allogeneic endothelial cells have been proposed to play decisive roles in fatal AR and in chronic allograft vasculopathy (Briscoe et al, 1998;Grau et al, 2001;Vos and Briscoe, 2000;Stehling et al, 2004;Reinders et al, 2006;Cailhier et al, 2006;Al-Lamki et al, 2008). A role in the reversion of AR remains to be defined.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys

et al. 2011

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“…Endothelial cells (ECs) express MHC class I and, in contrast to the human system, rat ECs do not express MHC class II constitutively [8,9]. But as non-professional APC they are able to increase their MHC class I and to induce MHC class II expression in response to IFNγ, thereby inducing direct allorecognition [10][11][12]. The MHC class II level has a major impact on the immunogenic potential of ECs, which is of great interest particularly in a transplantation setting [13].…”

Section: Introductionmentioning

confidence: 99%

Low immunogenicity of endothelial derivatives from rat embryonic stem cell-like cells

et al. 2009

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Embryonic stem cells (ESC) are suggested to be immune-privileged, but they carry the risk of uncontrolled expansion and malignancy. Upon differentiation they lose their tumor-forming capacity, but they become immunogenic by the expression of a normal set of MHC molecules. This immunogenicity might trigger rejection after application in regenerative therapies. In this study MHC expression of and immune responses to endothelial derivatives of rat embryonic stem cell-like cells (RESC) under inflammatory conditions were determined in comparison to primary rat aortic endothelial cells (ECs). Cellular as well as humoral allo-recognition was analyzed in vitro. In addition, immune reactions in vivo were assessed by allo-antibody production and determination of interferon-γ (IFNγ)-secreting allo-reactive T cells. RESC derivatives expressed low but significant levels of MHC class I, and no MHC class II. In response to IFNγ MHC class I expression was enhanced, while class II transactivator induction failed completely in these cells; MHC class II expression remained consistently absent. Functionally, the RESC derivatives showed a reduced allo-stimulatory capacity, protection against humoral allo-recognition in vitro and a slightly diminished susceptibility to cytotoxic T cell lysis. Furthermore, in vivo experiments demonstrated that these cells do not trigger host immune reactions, characterized by no allo-antibody production and no induction of allo-reactive memory T cells. Our results show that endothelial derivatives of RESC have a distinctive reduced immunogenic potency even under inflammatory conditions.

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Endothelial injury: cause and effect of alloimmune inflammation

Cited by 23 publications

References 135 publications

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys

Low immunogenicity of endothelial derivatives from rat embryonic stem cell-like cells

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