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Biomedicines
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Advances in Adenosine and Adenosine Receptors
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Advances in Adenosine and Adenosine Receptors

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 20643

Special Issue Editor

Dr. Julien Fromonot

E-Mail Website
Guest Editor
1. Laboratory of Biochemistry, Timone University Hospital, APHM, 13005 Marseille, France
2. Center for CardioVascular and Nutrition research (C2VN), INSERM, INRAE, Aix-Marseille University, Marseille, France
Interests: adenosinergic system; cardiovascular diseases; hypoxia; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During recent decades, adenosine and adenosine receptors have been extensively studied, and there is a growing understanding about the involvement of the adenosinergic system in human diseases. Because adenosine is rapidly produced by cellular metabolism and its four receptors are widely distributed in all tissues and cells, it is currently well-known that the adenosinergic system has major and pleiotropic effects in the cardiovascular, central nervous and immune systems. These dynamic research areas highlight new opportunities in the prognosis, diagnosis, and therapeutic strategies for cardiovascular diseases, including coronary artery disease, cardiac arrhythmia, stroke and syncope, neurodegenerative diseases including Alzheimer’s or Parkinson’s disease, and cancers, since the adenosinergic system could be targeted to improve anticancer therapies. Therefore, the aim of this Special Issue of Biomedicines entitled “Advances in Adenosine and Adenosine receptors” is to provide an overview of the state of the art and to promote new insights into adenosine and adenosine receptors in cancer, cardiovascular and neurodegenerative diseases. Both original articles and reviews consistent with this research topic will be considered for publication in this Special Issue.

Dr. Julien Fromonot
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adenosine
  • adenosine receptors
  • cardiovascular diseases
  • neurodegenerative diseases
  • cancer
  • immune system

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Published Papers (6 papers)

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Research

Jump to: Review

11 pages, 1486 KiB  
Article
Adenosine Receptors Profile in Fibromuscular Dysplasia
by Claire Guiol, Sarah El Harake, Julien Fromonot, Mohamed Chefrour, Marguerite Gastaldi, Yassine Alibouch, Maxime Doublier, Pierre Deharo, Gabrielle Sarlon, Marion Marlinge, Nathalie Lalevee, Régis Guieu and François Silhol
Biomedicines 2022, 10(11), 2831; https://doi.org/10.3390/biomedicines10112831 - 6 Nov 2022
Viewed by 1728
Abstract
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful [...] Read more.
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A1, A2A, and A2B receptor production by Western blot, in 67 patients (17 men and 50 women, mean (range) age 55 (29–77) years and 40 controls, 10 men and 30 women, mean (range) age 56 (37–70)). ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7–3) µmol/L vs. controls 0.6 (0.4–0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70 (0.90–2.40; arbitrary units) vs. controls = 1.03 (0.70–1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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11 pages, 1709 KiB  
Article
Plasma A2AR Measurement Can Help Physicians Identify Patients Suspected of Coronary Chronic Syndrome: A Pilot Study
by Franck Paganelli, Gabriel Cappiello, Soumeya Aliouane, Nathalie Kipson, Christine Criado, Khadidja Hamou, Jehuel Ntawanga, Erika Peroni, Maria Carreno, Lucas Methlin, Giovanna Mottola, Julien Fromonot, Pierre Deharo, Marine Gaudry, Marion Marlinge, Régis Guieu and Jean Ruf
Biomedicines 2022, 10(8), 1849; https://doi.org/10.3390/biomedicines10081849 - 1 Aug 2022
Cited by 1 | Viewed by 1524
Abstract
The evaluation of suspected coronary artery disease (CAD) in the medical community is challenging. Patients with suspected coronary chronic syndrome (CCS) are referred by the medical community to be assessed by specialists for the performance of noninvasive tests that have high rates of [...] Read more.
The evaluation of suspected coronary artery disease (CAD) in the medical community is challenging. Patients with suspected coronary chronic syndrome (CCS) are referred by the medical community to be assessed by specialists for the performance of noninvasive tests that have high rates of false positives and false negatives. While troponins are the gold standard for evaluate myocardial injuries, there is no biomarker to assess myocardial ischemia in patient populations with negative electrocardiography or without an increase in troponin level. A2A adenosine receptors control the coronary blood flow through its vasodilating properties. It has been shown that patients with CAD have a lower A2AR expression on peripheral blood mononuclear cells, suggesting a link between A2AR production and the severity of CAD. Herein, we present a new and innovative method of inhibition ELISA for A2AR in the plasma of patients who permit the evaluation of the amount of soluble A2AR. For this analysis, the total study sample was 54, including 31 patients with CAD with stenosis > 50% and a significant fractional flow reserve (FFR < 0.8) (Group 1) and 23 patients with normal or non-obstructive coronary arteries (stenosis < 50% and nonsignificant FFR > 0.8) (Group 2). The % inhibition (which is linked to the presence of soluble receptors) with the plasma of patients with FFR < 0.8 was significantly lower than that of patients with FFR > 0.8 (median [range]: 68% [20.7–86.9] vs. 83% [67–88.4]; p < 0.001). The ROC curve indicated a good sensitivity/specificity ratio with a cut off of 72.5% and an area under the curve of 0.87. In conclusion, a rapid ELISA to assess soluble A2AR in the plasma shows promise to screen patients suspected of having CAD. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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Review

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24 pages, 3581 KiB  
Review
Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation
by Baptiste Maille, Nathalie Lalevée, Marion Marlinge, Juliette Vahdat, Giovanna Mottola, Clara Degioanni, Lucille De Maria, Victor Klein, Franck Thuny, Frédéric Franceschi, Jean-Claude Deharo, Régis Guieu and Julien Fromonot
Biomedicines 2022, 10(11), 2963; https://doi.org/10.3390/biomedicines10112963 - 17 Nov 2022
Cited by 2 | Viewed by 7610
Abstract
Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative [...] Read more.
Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system’s signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential’s duration and induce the resting membrane’s potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors’ activation and whether this would be a cause or consequence of AF. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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10 pages, 804 KiB  
Review
Contribution of Adenosine in the Physiological Changes and Injuries Secondary to Exposure to Extreme Oxygen Pressure in Healthy Subjects
by Alain Boussuges, Jeremy Bourenne, Farid Eloufir, Julien Fromonot, Giovanna Mottola, Jean Jacques Risso, Nicolas Vallee, Fabienne Bregeon and Régis Guieu
Biomedicines 2022, 10(9), 2059; https://doi.org/10.3390/biomedicines10092059 - 24 Aug 2022
Cited by 1 | Viewed by 2256
Abstract
Climbers and aviators are exposed to severe hypoxia at high altitudes, whereas divers are exposed to hyperoxia at depth. The aim of this study was to report changes in the adenosinergic system induced by exposure to extreme oxygen partial pressures. At high altitudes, [...] Read more.
Climbers and aviators are exposed to severe hypoxia at high altitudes, whereas divers are exposed to hyperoxia at depth. The aim of this study was to report changes in the adenosinergic system induced by exposure to extreme oxygen partial pressures. At high altitudes, the increased adenosine concentration contributes to brain protection against hypoxia through various mechanisms such as stimulation of glycogenolysis for ATP production, reduction in neuronal energy requirements, enhancement in 2,3-bisphosphoglycerate production, and increase in cerebral blood flow secondary to vasodilation of cerebral arteries. In the context of mountain illness, the increased level of A2AR expression leads to glial dysfunction through neuroinflammation and is involved in the pathogenesis of neurological disorders. Nonetheless, a high level of adenosine concentration can protect against high-altitude pulmonary edema via a decrease in pulmonary arterial pressure. The adenosinergic system is also involved in the acclimatization phenomenon induced by prolonged exposure to altitude hypoxia. During hyperoxic exposure, decreased extracellular adenosine and low A2A receptor expression contribute to vasoconstriction. The resulting decrease in cerebral blood flow is considered a preventive phenomenon against cerebral oxygen toxicity through the decrease in oxygen delivery to the brain. With regard to lung oxygen toxicity, hyperoxia leads to an increase in extracellular adenosine, which acts to preserve pulmonary barrier function. Changes in the adenosinergic system induced by exposure to extreme oxygen partial pressures frequently have a benefit in decreasing the risk of adverse effects. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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23 pages, 2504 KiB  
Review
The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury
by Wei Ruan, Xinxin Ma, In Hyuk Bang, Yafen Liang, Jochen Daniel Muehlschlegel, Kuang-Lei Tsai, Tingting W. Mills, Xiaoyi Yuan and Holger K. Eltzschig
Biomedicines 2022, 10(8), 1939; https://doi.org/10.3390/biomedicines10081939 - 10 Aug 2022
Cited by 20 | Viewed by 4306
Abstract
Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF [...] Read more.
Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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10 pages, 877 KiB  
Review
Adenosine, Adenosine Receptors and Neurohumoral Syncope: From Molecular Basis to Personalized Treatment
by Régis Guieu, Clara Degioanni, Julien Fromonot, Lucille De Maria, Jean Ruf, Jean Claude Deharo and Michele Brignole
Biomedicines 2022, 10(5), 1127; https://doi.org/10.3390/biomedicines10051127 - 13 May 2022
Cited by 11 | Viewed by 2675
Abstract
Adenosine is a ubiquitous nucleoside that is implicated in the occurrence of clinical manifestations of neuro-humoral syncope (NHS). NHS is characterized by a drop in blood pressure due to vasodepression together with cardio inhibition. These manifestations are often preceded by prodromes such as [...] Read more.
Adenosine is a ubiquitous nucleoside that is implicated in the occurrence of clinical manifestations of neuro-humoral syncope (NHS). NHS is characterized by a drop in blood pressure due to vasodepression together with cardio inhibition. These manifestations are often preceded by prodromes such as headaches, abdominal pain, feeling of discomfort or sweating. There is evidence that adenosine is implicated in NHS. Adenosine acts via four subtypes of receptors, named A1 (A1R), A2A (A2AR), A2B (A2BR) and A3 (A3R) receptors, with all subtypes belonging to G protein membrane receptors. The main effects of adenosine on the cardiovascular system occurs via the modulation of potassium ion channels (IK Ado, K ATP), voltage-gate calcium channels and via cAMP production inhibition (A1R and A3R) or, conversely, through the increased production of cAMP (A2A/BR) in target cells. However, it turns out that adenosine, via the activation of A1R, leads to bradycardia, sinus arrest or atrioventricular block, while the activation of A2AR leads to vasodilation; these same manifestations are found during episodes of syncope. The use of adenosine receptor antagonists, such as theophylline or caffeine, should be useful in the treatment of some forms of NHS. The aim of this review was to summarize the main data regarding the link between the adenosinergic system and NHS and the possible consequences on NHS treatment by means of adenosine receptor antagonists. Full article
(This article belongs to the Special Issue Advances in Adenosine and Adenosine Receptors)
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