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.
Highlights
The importance of adenosine (ADO) and adenosine 50 -triphosphate (ATP) in regulating many biological functions has long been recognized, especially for their effects on the cardiovascular system [1,2,3,4,5,6,7,8,9,10]
It is known that ADO and adenosine -triphosphate (ATP) are key factors in the regulation of coronary blood flow [5,11,12,13], inhibiting platelet aggregation [14], protection of myocardium [10,15,16,17], neuromodulation [18,19,20,21,22,23,24,25], attenuating tissue necrosis [7,26], ischemic preconditioning [27,28,29,30,31,32], immunomodulation [33,34], energy metabolism [9,35,36,37,38], cancer biology signaling [39], and perhaps other functions as well, which maintain homeostasis of the cardiovascular system
Extracellular concentrations of ADO, such as those found in plasma under or below) because of rapid uptakeare bykept active nucleoside throughout vasculature, normal physiological conditions, very low becausethe of rapid uptakeand by by catabolism to other oxypurine metabolites, such as hypoxanthine and uric acid active nucleoside transporters throughout the vasculature, and by catabolism to other oxypurine
Summary
The importance of adenosine (ADO) and adenosine 50 -triphosphate (ATP) in regulating many biological functions has long been recognized, especially for their effects on the cardiovascular system [1,2,3,4,5,6,7,8,9,10]. After restoring the hypoxia to normal physiologic conditions, the released ADO is taken up rapidly transporters, subsequently back totransporters, ATP by ADO and adenylate kinases [46,47]. Such by endothelialand cells and RBC viaconverted the nucleoside and subsequently converted back to a salvage pathway is capable of recycling from readily, even in cells without. It discusses the opportunities, challenges, and obstacles of exploiting metabolism biomarker for cardiovascular protection and toxicities. It discusses the opportunities, in RBCs as a and target for drugofdevelopment andmetabolism precision medicine. Challenges, obstacles exploiting ATP in RBCs as a target for drug development and precision medicine
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