Advertisement

The Role of Adenosine and Its Degradation Enzymes – Adenosinedeaminase and Adenosinekinase in Pathogenesis of Vasovagal Syncope

Published:September 05, 2022DOI:https://doi.org/10.1016/j.ejim.2022.08.037

      Highlights

      • Adenosinergic system may play a role in the pathogenesis of vasovagal syncope.
      • Patients with tilt-induced VVS have higher serum adenosine than negative controls.
      • Adenosine is probably implicated predominantly in vasodepressoric type of VVS.
      • Patients with tilt-induced VVS have lower activity of adenosinedeaminase than controls.

      Abstract

      Introduction

      Adenosine is mediator regulating physiological and pathological processes in organism. It probably plays a role in pathogenesis of vasovagal syncopes (VVS), too. Adenosine, its receptors and degradation enzymes– adenosinedeaminase (ADA) and adenosinekinase (ADK), are called the adenosinergic system.

      Aim

      We aimed to evaluate serum levels of adenosine, ADA and ADK in patients with tilt-induced VVS and compare them to tlit-negative controls. Secondary aim was to compare the levels between the types of VVS and correlate them with hemodynamic parameters.

      Subjects and methods

      Altogether 132 individuals were involved in this study (age 39,88±15,64 years, 51 males). All patients underwent head up tilt test (HUTT) in differential diagnosis of syncope. Blood sampling was performed before and after HUTT. Baseline and stimulated serum levels of adenosine, ADA and ADK were evaluated by ELISA method.

      Results

      HUTT was positive in 91 patients (HUTT+), 41 individuals were negative (HUTT-). HUTT+ patients had higher baseline and stimulated adenosine levels, when compared to HUTT- population. The rise in adenosine was higher in HUTT+ group. On the other hand, the increase of ADA was significantly higher in HUTT- subjects. Among HUTT+ group, the highest adenosine was found during vasodepressoric VVS.

      Conclusion

      Adenosinergic system may play role in pathogenesis of VVS. Patients with VVS have higher adenosine levels, that may be caused by attenuated degradation. Adenosine seems to be involved predominantly in vasodepressoric type of VVS. Further research evaluating complex function of adenosinergic system in these patients is needed.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Headrick J.P.
        • Peart J.N.
        • Reichelt M.
        • et al.
        Adenosine and its receptors in the heart: regulation, retaliation and adaptation.
        Biochim Biophy Acta. 2010; 1808: 1413-1428
        • Adkisson W.O.
        • Benditt D.G
        Pathophysiology of reflex syncope: a review.
        J Cardiovasc Electrophysiol. 2017; 28: 1088-1097
        • Benditt D.G.
        • WO Adkisson
        Approach to the patient with syncope: venues, presentations, diagnoses.
        In Cardiol Clin. 2013; : 9-25
        • Vaddadi G.
        • Guo L.
        • Esler M.
        • et al.
        Recurrent postural vasovagal syncope: sympathetic nervous system phenotypes.
        In Circ Arrhythm Electrophysiol. 2011; 4: 711-718
        • Mitro P.
        • Rybarova E.
        • Zemberova E.
        • et al.
        Enhanced plasma catecholamine and cAMP response during the head-up tilt test in patients with vasovagal syncope.
        In Wien Klin Wochenschr. 2005; 117: 353-358
        • Fedorowski A.
        • Burri P.
        • Struck J.
        • et al.
        Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.
        In J Intern Med. 2013; 273: 359-367
        • Liao Y.
        • Xu W.R.
        • Li H.X.
        • et al.
        Plasma neuropeptide Y levels in vasovagal syncope in children.
        In Chin Med J (Engl). 2017; 130: 2778-2784
        • Bondanelli M.
        • Alboni P.
        • Margutti A.
        • et al.
        Plasma galanin response to head-up tilt in normal subjects and patients with recurrent vasovagal syncope.
        Metabolism. 2003; 52: 315-321
        • Hinghofer-Szalkay H.
        • Lackner H.K.
        • Rössler A
        Hormonal and plasma volume changes after presyncope.
        In Eur J Clin Invest. 2011; 41: 1180-1185
        • Williford N.N.
        • Chapleau M.W.
        • Olshansky B.
        Neurohormones in vasovagal syncope: are they important?.
        J Am Heart Assoc. 2019; 8e013129https://doi.org/10.1161/JAHA.119.013129
        • Saadjian A.Y.
        • Lévy S.
        • Franceschi F.
        • et al.
        Role of endogenous adenosine as a modulator of syncope induced during tilt testing.
        Circulation. 2002; 106: 569-574
        • Franceschi F.
        • By Y.
        • Peyrouse E.
        • et al.
        A2A adenosine receptor function in patients with vasovagal syncope.
        Europace. 2013; : 1328-1332
        • Borea P.A.
        • Gessi S.
        • Merighi S.
        • Vincenzi F.
        • Varani K.
        Pharmacology of adenosine receptors: the state of the art.
        Physiol Rev. 2018; 98: 1591-1625https://doi.org/10.1152/physrev.00049.2017
        • Burnstock G.
        Purinergic signaling in the cardiovascular system.
        Circ Res. 2017; 120: 207-228https://doi.org/10.1161/CIRCRESAHA.116.309726
        • Atif M.
        • Alsrhani A.
        • Naz F.
        • Imran M.
        • Imran M.
        • Ullah M.I.
        • et al.
        Targeting adenosine receptors in neurological diseases.
        Cell Reprogram. 2021; 23: 57-72https://doi.org/10.1089/cell.2020.0087
        • Reiss A.B.
        • Grossfeld D.
        • Kasselman L.J.
        • Renna H.A.
        • Vernice N.A.
        • Drewes W.
        • et al.
        Adenosine and the cardiovascular system.
        Am J Cardiovasc Drugs. 2019; 19: 449-464https://doi.org/10.1007/s40256-019-00345-5
        • Geldenhuys W.J.
        • Hanif A.
        • Yun J.
        • et al.
        Exploring adenosine receptor ligands: potential role in the treatment of cardiovascular diseases.
        Molecules. 2017; 22: 917
        • Pastor-Anglada M et Pérez-Torras S.
        Who is who in adenosine transport.
        Front Pharmacol. 2018; 9: 627
        • Eltzschig H.K.
        • Weissmuller T.
        • Mager A.
        • et al.
        Nucleotide metabolism and cell-cell interactions.
        Methods Mol Biol. 2006; 341: 73-87
        • Eltzschig H.K.
        • Faigle M.
        • Knapp S.
        • et al.
        Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26.
        Blood. 2006; 108: 1602-1610
        • Boison D.
        • Jarvis M.F.
        Adenosine kinase: a key regulator of purinergic physiology.
        Biochem Pharmacol. 2021; 187114321https://doi.org/10.1016/j.bcp.2020.114321
        • Bartoletti A.
        • Alboni P.
        • Ammirati F.
        • et al.
        The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope.
        Europace. 2000; 2: 339-342
        • Brignole M.
        • Menozzi C.
        • Del Rosso A.
        • et al.
        Is the type of cardiovascular response during tilt table testing useful for the choice of the treatment? the new VASIS classification.
        Card Arrhythm. 1999; 1: 449-462
        • Brignole M.
        • Moya A.
        • De Lange F.
        • et al.
        2018 ESC Guidelines for the diagnosis and management of syncope.
        Eur Heart J. 2018; : 1-69
        • Aste M.
        • Brignole M.
        Syncope and paroxysmal atrioventricular block.
        J Arrhythm. 2017; 33: 562-567
        • Brignole M.
        • Deharo J.C.
        • Guieu R.
        Syncope and idiopathic (paroxysmal) AV block.
        Cardiol Clin. 2015; 33: 441-447
        • Guieu R.
        • Degioanni C.
        • Fromonot J.
        • De Maria L.
        • Ruf J.
        • Deharo J.C.
        • et al.
        Adenosine, adenosine receptors and neurohumoral syncope: from molecular basis to personalized treatment.
        Biomedicines. 2022; 10: 1127https://doi.org/10.3390/biomedicines10051127
        • Jammes Y.
        • Joulia F.
        • Steinberg J.G.
        • Ravailhe S.
        • Delpierre S.
        • Condo J.
        • et al.
        Endogenous adenosine release is involved in the control of heart rate in rats.
        Can J Physiol Pharmacol. 2015; 93: 667-675https://doi.org/10.1139/cjpp-2015-0042
        • Sutton R.
        The value of tilt testing and autonomic nervous system assessment.
        In Cardiol Clin. 2015; 33: 357-360
        • Adkisson W.O.
        • Benditt D.G
        Pathophysiology of reflex syncope: a review.
        J Cardiovasc Electrophysiol. 2017; 28: 1088-1097
        • Waxman M.B.
        • Asta J.A.
        Role of adenosine receptors in the paradoxic bradycardia response of rats to inferior vena cava occlusion during an infusion of isoproterenol.
        Circulation. 1998; 98: 1228-1235
        • Borowiec A.
        • Lechward K.
        • Tkacz-Stachowska K.
        • Składanowski A.C.
        Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5′-nucleotidases.
        Acta Biochim Pol. 2006; 53: 269-278
        • Karmouty-Quintana H.
        • Xia Y.
        • Blackburn M.R.
        Adenosine signaling during acute and chronic disease states.
        J Mol Med (Berl). 2013 Feb; 91: 173-181https://doi.org/10.1007/s00109-013-0997-1
        • Deharo J.C.
        • Brignole M.
        • Guieu R.
        Adenosine and neurohumoral syncope.
        Minerva Med. 2022 Apr; 113: 243-250https://doi.org/10.23736/S0026-4806.21.07537-6