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Letter to Editor

Prophylactic use of mTOR inhibitors and other immunosuppressive agents in heart transplant patients

Cellular & Molecular Immunology volume 12, pages 122–124 (2015)Cite this article

Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances have been made in the prevention and treatment of acute transplant rejection, accelerated cardiac allograft vasculopathy (CAV) still limits the long-term success of heart transplantation. CAV is a rapidly progressive form of atherosclerosis described by vascular remodeling of the graft coronary arteries that occurs uniquely in transplant recipients. In the early stages, CAV is characterized by intimal proliferation, while luminal stenosis of epicardial branches, occlusion of smaller arteries and myocardial infarction occur in the later stages.1 These events are the results of cumulative endothelial injuries induced by nonspecific insults, such as ischemia–reperfusion injury, as well as by alloimmune responses. Thus, innate and adaptive immune responses are involved in the pathogenesis of this disease, as supported by the evidence that syngeneic transplants and transplants into immune deficient mice (such as RAG 1−/− mice) fail to develop CAV.2,3

Neutrophils are commonly associated with ischemia reperfusion injury.4,5,6 They are recruited to transplants through inflammatory chemokines secreted by the graft vasculature, such as tumor-necrosis factor (TNF) and interleukin-1 (IL-1), expressed during reperfusion.6 King et al. investigated the role of neutrophils in CAV development in a mouse model. In this study, aortic transplants were performed in the presence of therapeutic levels of cyclosporine A and subsequently aortas were harvested at different times after transplantation. The authors reported that the peaks of neutrophil flux into the media occurred at 1 day and 1 week post-transplant and correlated with medial smooth muscle cell (SMC) destruction. This loss was significantly reduced by neutrophil depletion.6 In the same view, So et al.7 investigated the role of neutrophils in the loss of SMC at 1 day and the failure to recover by 2 weeks in the presence of prolonged (60-min) cold ischemia in neutrophil loss-of-function recipient B6 mice (NOX2−/−). They first observed that the loss of SMC was lower in grafts transplanted into NOX2−/− as compared to wild-type B6 recipients. Moreover, grafts transplanted into NOX2−/− recipients exhibited significant SMC repopulation at 2 weeks after transplant, despite exposure to 60-min cold ischemia.

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Authors and Affiliations

  1. Clinica di Oncologia Medica, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy

    Matteo Santoni & Stefano Cascinu

  2. Medical Oncology, ‘G.B. Rossi’ Academic Hospital, University of Verona, Verona, Italy

    Francesco Massari

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  1. Matteo Santoni
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  2. Francesco Massari
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  3. Stefano Cascinu
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Correspondence to Matteo Santoni.

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Santoni, M., Massari, F. & Cascinu, S. Prophylactic use of mTOR inhibitors and other immunosuppressive agents in heart transplant patients. Cell Mol Immunol 12, 122–124 (2015). https://doi.org/10.1038/cmi.2014.27

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