Combination of clopidogrel and everolimus completely abolished the development of transplant arteriosclerosis

Eckl S, Heim C, Abele-Ohl S, Hoffmann J, Weyand M, Ensminger SM, Weyand M (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Transplantationsmedizin Pabst Science Publishers

Book Volume: 21

Pages Range: 145-

Journal Issue: SUPPL. 2

Abstract

Introduction: Our group has previously shown that platelet inhibition with clopidogrel reduced the formation of transplant arteriosclerosis (TxA). The aim of this study was to investigate whether a combination of cyclosporine or everolimus with clopidogrel has a beneficial effect on the development of TxA. Methods: Fully allogeneic C57BL/6 (H2b) donor aortas were transplanted into CBA (H2k) recipients. Recipient mice were treated with cyclosporine (2mg/kg/d) and everolimus (0,05mg/kg/d) alone or in combination with clopidogrel (1mg/kg/d). Grafts were analysed by histology and morphometry on day 30 after transplantation. Results: In mice treated with clopidogrel alone, TxA was reduced as compared to untreated controls (intima proliferation 57%+/-13% vs. 79%+/-8% [control]/n=5). Daily application of everolimus significantly reduced the development of TxA compared to untreated controls (intima proliferation of 27% +/- 10% vs. 79% +/-8% [control], n=5). Strikingly, combination of clopidogrel and everolimus almost completely abolished the formation of TxA (intima proliferation: 14% +/- 10% vs. 79% +/- 8% [control], n = 5). In contrast, daily application of cyclosporine alone did not reduce the development of TxA compared to controls (intima proliferation: 74% +/- 7% vs. 79% +/- 8% [control], n=5). In addition combination of cyclosporine and clopidogrel compared with clopidogrel alone showed no additive effect. Conclusion: These results demonstrate that combination of clopidogrel and everolimus can completely abolish the development of TxA in a mouse aortic allograft model. Our findings have also important clinical implications as patients suffering from TxA after cardiac transplantation may benefit from treatment with a combination of these drugs.

Authors with CRIS profile

Christian Heim Department of Cardiac Surgery Michael Weyand Lehrstuhl für Herzchirurgie

How to cite

APA:

Eckl, S., Heim, C., Abele-Ohl, S., Hoffmann, J., Weyand, M., Ensminger, S.M., & Weyand, M. (2009). Combination of clopidogrel and everolimus completely abolished the development of transplant arteriosclerosis. Transplantationsmedizin, 21(SUPPL. 2), 145-.

MLA:

Eckl, S., et al. "Combination of clopidogrel and everolimus completely abolished the development of transplant arteriosclerosis." Transplantationsmedizin 21.SUPPL. 2 (2009): 145-.

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