Is mycophenolate more than just an immunosuppressant? An overview

Iyer, Abishek and Brown, Lindsay (2009) Is mycophenolate more than just an immunosuppressant? An overview. Indian Journal of Biochemistry and Biophysics, 46 (1). pp. 25-30. ISSN 0301-1208

Abstract

The development of immunosuppressant compounds, such as cyclosporine and tacrolimus was crucial to the success of transplant surgery and for treatment of autoimmune diseases. However, immunosuppressant therapy may increase the concentrations of reactive oxygen species (ROS), inducing oxidative damage such as an increased vascular damage. The major source of ROS in the vascular endothelial cells is NADPH oxidase. The subunit structure and function of this enzyme complex in vascular cells differs from that in phagocytic leucocytes. The enzyme subunits Nox1, Nox2 and Nox4 are only found in vascular cells. The GTP-dependent protein subunit Rac 1 needs to be activated for this enzyme to function. Inhibiting this protein subunit should reduce NADPH oxidase-induced oxidative stress. In the cardiovascular system, oxidative stress is observed as hypertension, hypertrophy, fibrosis, conduction abnormalities and endothelial dysfunction, as well as cardiac allograft vasculopathy in transplant patients. In contrast to cyclosporine and tacrolimus, the immunosuppressant mycophenolate inhibits the Rac 1 subunit thus inhibiting NADPH oxidase in the vasculature. This may reduce oxidative stress, prevent the development of cardiac allograft vasculopathy, decrease the deterioration of vascular function and improve cardiovascular function chronically in transplant patients. This overview discusses whether this anti-oxidant immunosuppressive property could translate into a more general protective role for mycophenolate in the prevention of cardiovascular disease.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Items in NISCAIR Online Periodicals Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Depositing User: Professor Lindsay Brown
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 12 Jun 2010 05:21
Last Modified: 08 Oct 2014 23:21
Uncontrolled Keywords: mycophenolate; immunosuppressants; oxidative stress; NADPH oxidase; cardiovascular disease
Fields of Research (FOR2008): 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
Socio-Economic Objective (SEO2008): E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
URI: http://eprints.usq.edu.au/id/eprint/7752

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