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- W2044317877 endingPage "156" @default.
- W2044317877 startingPage "141" @default.
- W2044317877 abstract "Cardiac allograft vasculopathy (CAV) occurs within 5 years of transplantation surgery and represents the main cause of death in long-term heart transplant survivors. The detailed pathogenesis of CAV is unknown, but there are strong indications that immunologic mechanisms, which are regulated by nonimmunologic factors, are the major cause of this phenomenon. Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection. The mechanism of action of CsA involves initial binding to cyclophilin to form a complex that then inhibits calcineurin (CN), leading to reduced interleukin (IL)-2 production as part of the signal transduction pathway for the activation of B-lymphocytes and T-lymphocytes. Based on this proposed mechanism, it was expected that CsA should be an effective strategy in attenuating the host immune response against transplanted allograft tissue; however, CsA has not changed the outcome of CAV. Several mechanisms have been suggested for the ineffectiveness of CsA in long-term prevention of CAV. For example, routine therapeutic doses of CsA may block CN incompletely (50%), whereas complete blockade requires doses that are not clinically tolerable. Another explanation is the possible activation of T-cell receptors directly (CN independent) by the immune response, which induces protein kinase C theta (PKCtheta) and leads to IL-2 production and immune rejection. Moreover, there may be a role for nonimmunologic mechanisms, such as complement, which cannot be controlled by CsA, or CsA may cause hypercholesterolemia or induce overexpression of transforming growth factor-beta (TGF-beta). This review also compares the effect of CsA with other immunosuppressants in allograft artery preservation and their clinical efficacy." @default.
- W2044317877 created "2016-06-24" @default.
- W2044317877 creator A5040952783 @default.
- W2044317877 creator A5058694015 @default.
- W2044317877 creator A5081302566 @default.
- W2044317877 date "2003-11-01" @default.
- W2044317877 modified "2023-10-17" @default.
- W2044317877 title "Immunosuppression and transplant vascular disease: benefits and adverse effects" @default.
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