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Metabolites 2018, 8(2), 30; https://doi.org/10.3390/metabo8020030

Adenosine 5′-Triphosphate Metabolism in Red Blood Cells as a Potential Biomarker for Post-Exercise Hypotension and a Drug Target for Cardiovascular Protection

Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
The paper was presented in part as a keynote at the International Conference on Hypertension and Healthcare, Toronto, ON, Canada, 11–12 August 2016 and also at the 2nd International Electronic Conference on Metabolomics, 20–27 November 2017.
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Received: 6 April 2018 / Revised: 27 April 2018 / Accepted: 29 April 2018 / Published: 2 May 2018
(This article belongs to the Special Issue Metabolomics and/or Biomarkers for Drug Discovery)
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Abstract

The importance of adenosine and ATP in regulating many biological functions has long been recognized, especially for their effects on the cardiovascular system, which may be used for management of hypertension and cardiometabolic diseases. In response to ischemia and cardiovascular injury, ATP is broken down to release adenosine. The effect of adenosine is very short lived because it is rapidly taken up by erythrocytes (RBCs), myocardial and endothelial cells, and also rapidly catabolized to oxypurine metabolites. Intracellular adenosine is phosphorylated back to adenine nucleotides via a salvage pathway. Extracellular and intracellular ATP is broken down rapidly to ADP and AMP, and finally to adenosine by 5′-nucleotidase. These metabolic events are known to occur in the myocardium, endothelium as well as in RBCs. Exercise has been shown to increase metabolism of ATP in RBCs, which may be an important mechanism for post-exercise hypotension and cardiovascular protection. The post-exercise effect was greater in hypertensive than in normotensive rats. The review summarizes current evidence in support of ATP metabolism in the RBC as a potential surrogate biomarker for cardiovascular protection and toxicities. It also discusses the opportunities, challenges, and obstacles of exploiting ATP metabolism in RBCs as a target for drug development and precision medicine. View Full-Text
Keywords: ATP; adenosine; metabolism; exercise; cardiovascular protection; drug target ATP; adenosine; metabolism; exercise; cardiovascular protection; drug target
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Yeung, P.K.; Kolathuru, S.S.; Mohammadizadeh, S.; Akhoundi, F.; Linderfield, B. Adenosine 5′-Triphosphate Metabolism in Red Blood Cells as a Potential Biomarker for Post-Exercise Hypotension and a Drug Target for Cardiovascular Protection. Metabolites 2018, 8, 30.

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