Ribose supplementation alone or with elevated creatine does not preserve high energy nucleotides or cardiac function in the failing mouse heart

Faller, K. M.E., Medway, D. J., Aksentijevic, D., Sebag-Montefiore, L., Schneider, J. E., Lygate, C. A. and Neubauer, S. (2013) Ribose supplementation alone or with elevated creatine does not preserve high energy nucleotides or cardiac function in the failing mouse heart. PLoS ONE, 8(6), e66461. (doi: 10.1371/journal.pone.0066461) (PMID:23823183) (PMCID:PMC3688916)

Abstract

Background: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE). Methods and Results: Four groups were studied: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8–14%) in all infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32–47% increased mass). Ejection fraction closely correlated with infarct size independently of treatment (r2 = 0.63, p<0.0001), but did not correlate with myocardial creatine or TAN levels. Conclusion: Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically failing mouse heart and that alternative strategies to preserve TAN pool should be investigated.

• Item Type: Articles
• Additional Information: This research was supported by the British Heart Foundation (BHF, Grants FS/07/065 and RG/10/002/28187, FS11/50/29038) http://www.bhf.org.uk. Additional funding for the Visualsonics ultrasound system was provided by the BHF Centre of Research Excellence, Oxford (RE/08/004). The research centre where this work was conducted is funded by a Wellcome Trust Core Award (090532/Z/09/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Faller, Ms Kiterie
• Authors: Faller, K. M.E., Medway, D. J., Aksentijevic, D., Sebag-Montefiore, L., Schneider, J. E., Lygate, C. A., and Neubauer, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2013 Faller et al.
• First Published: First published in PLoS ONE 8(6): e66461
• Publisher Policy: Reproduced under a Creative Commons License