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Biliverdin reductase in cardiovascular inflammation

Sangha, Jason (2011)
M.Phil. thesis, University of Birmingham.

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Abstract

Biliverdin Reductase (BVR) functions downstream of Heme Oxygenase 1 (HO-1) in the process of heme degradation and catalyses the reduction of biliverdin to bilirubin. For over thirty years, BVR was regarded as rather a trivial enzyme whose only known function was to aid heme disposal. Over the last decade however, it has become increasingly clear that BVR is pleiotropic in function and for example, functions as a dual-specificity protein kinase and also as a transcription factor. The bile pigment bilirubin is now known to possess potent anti-inflammatory and antioxidant effects, and this finding is underscored clinically by the observation that mild hyperbilirubinemia, due to Gilbert’s syndrome, protects patients against cardiovascular diseases associated with atherosclerosis. However a number of studies have suggested that BVR, aside from its bilirubin generating capacity, is pro-inflammatory. In the present study, we show that BVR acts in an anti-inflammatory manner in the endothelium; by increasing eNOS activation and nitric oxide release, inducing HO-1 protein expression and by inhibiting TNFα-induced leukocyte-endothelium interaction. These highly novel findings give credence to future therapeutic strategies aiming to modulate BVR activity in vivo in the fight against chronic inflammatory diseases such as atherosclerosis.

Type of Work:M.Phil. thesis.
Supervisor(s):Ahmed, Asif
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine, Centre for Cardiovascular Science
Subjects:RC Internal medicine
Institution:University of Birmingham
ID Code:1206
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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