Characterization of adenosine A2 receptors in peripheral blood mononuclear cells of patients with fibromuscular dysplasia

Silhol, F.; Marlinge, Marion; Guiol, Claire; Chefrour, Mohamed; Mace, Patrick; Criado, C. Fernandez; Kipson, Nathalie; Vaı̈sse, B.; Vairo, Donato; Sarlon, Gabrielle; Ruf, Jean; Donnet, Anne; Bruzzese, Laurie; Mottola, Giovanna; Guieu, Régis; Fenouillet, Emmanuel

doi:10.1038/s41440-019-0379-3

Cited by 4 publications

(5 citation statements)

References 11 publications

(9 reference statements)

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“…ROC curves indicate a good predictive value for the A 2B R production with a cut-off 1.23 associated with a good sensitivity of A 2B R overproduction. Similar data have previously been reported in a pilot study including a weak number of FMD patients that did not permit to establish ROC curves [ 10 ].…”

Section: Discussionsupporting

confidence: 85%

Adenosine Receptors Profile in Fibromuscular Dysplasia

Guiol

Harake²,

Fromonot

et al. 2022

Biomedicines

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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.

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Section: Discussionsupporting

confidence: 85%

Adenosine Receptors Profile in Fibromuscular Dysplasia

Guiol

Harake²,

Fromonot

et al. 2022

Biomedicines

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“…Indeed, beneficial effects of A 1 R or A 2B R KO were limited to females [155]. High APL was found in patients with essential hypertension [169], while high A 2B receptor expression was found in patients with hypertension associated with fibromuscular dysplasia [169].…”

Section: Adenosine and Systemic Hypertensionmentioning

confidence: 99%

Adenosine and the Cardiovascular System: The Good and the Bad

Guieu

Deharo

Maille

et al. 2020

JCM

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Adenosine is a nucleoside that impacts the cardiovascular system via the activation of its membrane receptors, named A1R, A2AR, A2BR and A3R. Adenosine is released during hypoxia, ischemia, beta-adrenergic stimulation or inflammation and impacts heart rhythm and produces strong vasodilation in the systemic, coronary or pulmonary vascular system. This review summarizes the main role of adenosine on the cardiovascular system in several diseases and conditions. Adenosine release participates directly in the pathophysiology of atrial fibrillation and neurohumoral syncope. Adenosine has a key role in the adaptive response in pulmonary hypertension and heart failure, with the most relevant effects being slowing of heart rhythm, coronary vasodilation and decreasing blood pressure. In other conditions, such as altitude or apnea-induced hypoxia, obstructive sleep apnea, or systemic hypertension, the adenosinergic system activation appears in a context of an adaptive response. Due to its short half-life, adenosine allows very rapid adaptation of the cardiovascular system. Finally, the effects of adenosine on the cardiovascular system are sometimes beneficial and other times harmful. Future research should aim to develop modulating agents of adenosine receptors to slow down or conversely amplify the adenosinergic response according to the occurrence of different pathologic conditions.

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“…A high adenosine plasma concentration could also be a consequence of energy use in specific underlying cardiovascular conditions, including hypertension [ 138 , 139 ], chronic heart failure [ 13 , 140 ] or vagal syncope [ 141 , 142 ]. These are especially known to be AF risk factors.…”

Section: Arrhythmogenic Effects Of the Adenosinergic Systemmentioning

confidence: 99%

“…Moreover, all three AF risk factors also induce specific adenosinergic system remodeling. Especially in patients suffering from essential hypertension, an A 2A R overexpression was described in PBMCs [ 139 ]. Because of the vasodilator effect of A 2A R, it was hypothesized that the A 2A R overexpression was a compensatory mechanism of high blood pressure [ 176 ].…”

Section: Association Between Atrial Fibrillation Risk Factors and The...mentioning

confidence: 99%

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

et al. 2022

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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.

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Characterization of adenosine A2 receptors in peripheral blood mononuclear cells of patients with fibromuscular dysplasia

Cited by 4 publications

References 11 publications

Adenosine Receptors Profile in Fibromuscular Dysplasia

Adenosine Receptors Profile in Fibromuscular Dysplasia

Adenosine and the Cardiovascular System: The Good and the Bad

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

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