Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II

Hanif, Ahmad; Agba, Stephanie; Ledent, Catherine; Tilley, Stephen L.; Morisseau, Christophe; Nayeem, Mohammed

doi:10.1007/s11010-021-04049-w

Cited by 7 publications

(12 citation statements)

References 46 publications

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“…61,62 Moreover, previous studies also showed the close association between ADORA2A and Ang in angiogenesis. 63,64 Therefore, we speculate that Ang may affect placental angiogenesis as a target gene of adenosine-ADORA2A signaling. We also found that Ang overexpression could rescue the angiogenesis inhibited by ADORA2A knockdown under adenosine treatment.…”

Section: Discussionmentioning

confidence: 95%

Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway

Xiang

Feng

et al. 2023

ATVB

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BACKGROUND: Abnormal placental angiogenesis is an important cause of fetal intrauterine growth restriction (IUGR), but its underlying mechanisms and therapies remain unclear. Adenosine and its mediated signaling has been reported to be associated with the development of angiogenesis. However, whether the adenosine-related signaling plays a role in modulating angiogenesis in placenta and the IUGR pregnancy outcomes remains unclear. METHODS: The angiogenesis and adenosine signaling expressions in normal and IUGR placentas were detected in different species. And the role of adenosine in regulating IUGR pregnancy outcomes was evaluated using diet-induced IUGR mouse model. Molecular mechanisms underlying adenosine-induced angiogenesis were investigated by in vitro angiogenesis assays and in vivo Matrigel plug assays. RESULTS: Here, we demonstrated poor angiogenesis and low adenosine concentration and downregulated expression of its receptor A2a (ADORA2A [adenosine A2a receptor]) in IUGR placenta. Additionally, the beneficial effects of adenosine in improving IUGR pregnancy outcomes were revealed in a diet-induced IUGR mouse model. Moreover, adenosine was found to effectively improve adenosine signaling and angiogenesis in IUGR mice placenta. Mechanistically, by using angiogenesis assays in vitro and in vivo, adenosine was shown to activate ADORA2A to promote the phosphorylation of Stat3 (signal transducer and activator of transcription 3) and Akt (protein kinase B), resulting in increased Ang (angiogenin)-dependent angiogenesis. CONCLUSIONS: Collectively, this study uncovers an unexpected mechanism of promoting placental angiogenesis by adenosine-ADORA2A signaling and advances the translation of this signaling as a prognostic indicator and therapeutic target in IUGR treatment.

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Section: Discussionmentioning

confidence: 95%

Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway

Xiang

Feng

et al. 2023

ATVB

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“…Adenosine A2A receptor (ADORA2A), which belongs to the family of adenosine receptors that are most abundant in the brain, has been reported to contribute to neuroinflammation and synaptic and neuronal damage (18) and is considered a biomarker of brain diseases. A study using adenosine A2A receptor-null (Adora2a-/-) mice demonstrated its role in the coronary reactive hyperemic response and vascular contraction (19). Another study using Adora2a-/mice showed that inactivation of endothelial ADORA2A protected mice from cerebral ischemia-induced brain injury and improved post-stroke outcomes through antiinflammatory effects and blockade of NLRP3 inflammasome activity (20).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms for the prevention and promoting the recovery from ischemic stroke by nutraceutical laminarin: A comparative transcriptomic approach

et al. 2022

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Stroke is the second leading cause of death and a major cause of disability worldwide. Ischemic stroke caused by atherosclerosis accounts for approximately 87% of all stroke cases. Ischemic stroke is a preventable disease; therefore, a better understanding of the molecular mechanisms underlying its pathogenesis and recovery processes could provide therapeutic targets for drug development and reduce the associated mortality rate. Laminarin, a polysaccharide, is a nutraceutical that can be found in brown algae. Accumulating evidence suggests that laminarin could reduce the detrimental effects of neuroinflammation on brain damage after stroke. However, the molecular mechanism underlying its beneficial effects remains largely unknown. In the present study, we used a middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomics to investigate the molecular targets and pathways involved in the beneficial effects of laminarin on ischemic stroke. Our results show the involvement of laminarin targets in biological processes related to blood circulation, oxygen supply, and anti-inflammatory responses in the normal brain. More importantly, laminarin treatment attenuated brain damage and neurodeficits caused by ischemic stroke. These beneficial effects are controlled by biological processes related to blood vessel development and brain cell death through the regulation of canonical pathways. Our study, for the first time, delineated the molecular mechanisms underlying the beneficial effects of laminarin on ischemic stroke prevention and recovery and provides novel therapeutic targets for drug development against ischemic stroke.

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“…Renin-angiotensin system (RAS) is highly affected in Covid-19 owing to the down-regulation of ACE2 and interconnected with the progress of ALI, ARDS, and injury in multiple organs [ 47 ]. It has been reported recently that DIP reduces RAS and circulating AngII serum levels through an AD-dependent pathway [ 46 , 47 ] or PDE inhibition pathway [ 48 , 49 ]. Furthermore, DIP also mitigates Covid-19-induced complications like acute kidney injury [ 50 ], acute coronary syndrome [ 51 ], acute brain injury [ 52 ], and cytokine storm-mediated multi-organ injury [ 53 , 54 ].…”

Section: Adenosinergic Pathway and Dip In Covid-19mentioning

confidence: 99%

Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail

Al-Kuraishy

Al-Gareeb

Elekhnawy

et al. 2022

Egypt J Med Hum Genet

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Background Coronavirus disease 2019 (Covid-19) is an infectious worldwide pandemic triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2). This pandemic disease can lead to pro-inflammatory activation with associated acute lung injury and acute respiratory distress syndrome. Main body of the abstract SARS-CoV-2 infection is linked with inhibition of adenosine and activation of phosphodiesterase. Dipyridamole (DIP) is a nucleoside transport and phosphodiesterase inhibitor so that it may potentially affect SARS-CoV-2 infection and its accompanying inflammations. Therefore, the primary objective of this mini-review study was to elucidate the potential beneficial impacts of DIP on the adenosinergic pathway in Covid-19. A systemic search was done using online databases with relevant keywords. The findings of the present study illustrated that DIP directly or indirectly, through augmentation of adenosine and inhibition of phosphodiesterase, mitigates Covid-19 outcomes. Conclusion Our study concluded that DIP has a potential therapeutic effect in the management and treatment of Covid-19. This could be attained either directly, through anti-SARS-CoV-2, anti-inflammatory, and anti-platelets properties, or indirectly, through augmentation of extracellular adenosine, which has anti-inflammatory and immune-regulatory effects. However, extensive randomized clinical trials, and clinical and prospective research in this area are required to demonstrate the safety and therapeutic efficacy of DIP and adenosine modulators in the treatment of Covid-19.

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Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II

Cited by 7 publications

References 46 publications

Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway

Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway

Molecular mechanisms for the prevention and promoting the recovery from ischemic stroke by nutraceutical laminarin: A comparative transcriptomic approach

Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail

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