Development of a combined cardiac and aortic transplant model to investigate the development of transplant arteriosclerosis in the mouse

Ensminger, Stephan; Billing, J. Stephen; Morris, Peter J.; Wood, Kathryn J.

doi:10.1016/s1053-2498(00)00195-9

Cited by 39 publications

(31 citation statements)

References 23 publications

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“…For the morphometric analysis of the degree of intimal thickening, the area within the lumen and the internal elastic lamina was circumscribed manually. A digitized image of each section was captured and measured as previously described (23). All image analysis was carried out using ANAlysis R Image Analysis software (Olympus, Hamburg, Germany).…”

Section: Morphometric Analysis Of the Mammary Artery Graftmentioning

confidence: 99%

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Abele-Ohl

Leis

Wollin

et al. 2012

American Journal of Transplantation

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Section: Morphometric Analysis Of the Mammary Artery Graftmentioning

confidence: 99%

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Abele-Ohl

Leis

Wollin

et al. 2012

American Journal of Transplantation

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“…Furthermore, we have demonstrated the suitability of the aortic graft to study transplant arteriosclerosis as compared with the vascularized cardiac allograft model (17). The aortic graft has the advantage that it is a nonparenchymal transplant, which therefore contains only a minimal number of donor-derived passenger leukocytes that might be able to interfere in this system by initiating an alloresponse.…”

mentioning

confidence: 99%

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

Ensminger

Spriewald

Sorensen

et al. 2001

The Journal of Immunology

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Blockade of the CD40-CD154 pathway can inhibit CD4+ T cell activation but is unable to prevent immune responses mediated by CD8+ T cells. However, even in the absence of CD8+ T cells, inhibition of the CD40-CD154 pathway is insufficient to prevent the development of transplant arteriosclerosis. This study investigated the mechanisms of transplant arteriosclerosis in the absence of the CD40 pathway. C57BL/6 CD40−/− (H2b) recipients were transplanted with MHC-mismatched BALB/c (H2d) aortas. Transplant arteriosclerosis was evident in both CD40−/− and CD40+/− mice (intimal proliferation was 59 ± 5% for CD40−/− mice vs 58 ± 4% for CD40+/− mice) in the presence or absence of CD8+ T cells (intimal proliferation was 46 ± 7% for CD40−/− anti-CD8-treated mice vs 50 ± 10% for CD40+/− anti-CD8-treated mice), confirming that CD8+ T cells are not essential effector cells for the development of this disease. In CD40−/− recipients depleted of CD8+ T cells, the number of eosinophils infiltrating the graft was markedly increased (109 ± 24 eosinophils/grid for CD40−/− anti-CD8-treated mice vs 28 ± 7 for CD40+/− anti-CD8-treated mice). The increased presence of eosinophils correlated with augmented intragraft production of IL-4. To test the hypothesis that IL-4 was responsible for the intimal proliferation, CD8 T cell-depleted CD40−/− recipients were treated with anti-IL-4 mAb. This resulted in significantly reduced eosinophil infiltration into the graft (12 ± 5 eosinophils/grid for CD40−/− anti-CD8+, anti-IL-4-treated mice vs 109 ± 24 for CD40−/− anti-CD8-treated mice), intragraft eotaxin, CCR3 mRNA production, and the level of intimal proliferation (18 ± 5% for CD40−/− anti-CD8+-, anti-IL-4-treated mice vs 46 ± 7% for CD40−/− anti-CD8-treated mice). In conclusion, elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8+ T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

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“…7 Chronic rejection models have been used widely to investigate the pathogenesis of chronic vascular rejection. [8][9][10][11][12][13] In conclusion, size discrepancy between donor and recipient aortas is not in obstacle in a mouse heterotopic aortic transplant if the sleeve technique is used. The approach we report in this study will help develop a better heterotopic aortic transplant model for basic and translational research on chronic rejection.…”

Section: Discussionmentioning

confidence: 85%

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2014

Exp Clin Transplant

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Objectives: We sought to develop a better approach in establishing a heterotopic aortic transplant model. Materials and Methods: We used "sleeve" operation and set up 2 heterotopic aortic transplant experimental groups (groups 1 and 2). In group 1, donors (BALB/c (H-2 d ) mice; weight, 25-30 g) had the same weight as the recipients (C57BL/6 (H-2 d ) mice; weight, 25-30 g); in group 2, donors had lower weights (BALB/c (H-2d) mice, weight, 15-20 g). Grafts were examined macroscopically and histologically 60 days after the transplant. Results: The thrombosis incidence was 10% in group 1 (5 of 50) and 2% in group 2 (1 of 50) (P < .05).Intestinal obstructions led to a high mortality rate in both groups: 8% in group 1 and 10% in group 2 (P < .05). Conclusions:The issue of size discrepancy between donor and recipient aortas is not a problem in a heterotopic aortic transplant model with the use of a sleeve technique, while the high incidence of intestinal obstructions must be considered.

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Development of a combined cardiac and aortic transplant model to investigate the development of transplant arteriosclerosis in the mouse

Cited by 39 publications

References 23 publications

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

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