{"doi":"10.1161/jaha.122.028421","title":"Adenosine A <sub>2A</sub> Receptor Regulates microRNA‐181b Expression in Aorta: Therapeutic Implications for Large‐Artery Stiffness","abstract":"Background The identification of large‐artery stiffness as a major, independent risk factor for cardiovascular disease–associated morbidity and death has focused attention on identifying therapeutic strategies to combat this disorder. Genetic manipulations that delete or inactivate the translin/trax microRNA‐degrading enzyme confer protection against aortic stiffness induced by chronic ingestion of high‐salt water (4%NaCl in drinking water for 3 weeks) or associated with aging. Therefore, there is heightened interest in identifying interventions capable of inhibiting translin/trax RNase activity, as these may have therapeutic efficacy in large‐artery stiffness. Methods and Results Activation of neuronal adenosine A 2A receptors (A 2A Rs) triggers dissociation of trax from its C‐terminus. As A 2A Rs are expressed by vascular smooth muscle cells (VSMCs), we investigated whether stimulation of A 2A R on vascular smooth muscle cells promotes the association of translin with trax and, thereby increases translin/trax complex activity. We found that treatment of A7r5 cells with the A 2A R agonist CGS21680 leads to increased association of trax with translin. Furthermore, this treatment decreases levels of pre‐microRNA‐181b, a target of translin/trax, and those of its downstream product, mature microRNA‐181b. To check whether A 2A R activation might contribute to high‐salt water–induced aortic stiffening, we assessed the impact of daily treatment with the selective A 2A R antagonist SCH58261 in this paradigm. We found that this treatment blocked aortic stiffening induced by high‐salt water. Further, we confirmed that the age‐associated decline in aortic pre‐microRNA‐181b/microRNA‐181b levels observed in mice also occurs in humans. Conclusions These findings suggest that further studies are warranted to evaluate whether blockade of A 2A Rs may have therapeutic potential in treating large‐artery stiffness.","journal":"Journal of the American Heart Association","year":2023,"id":377203,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1140628,"name":"Tomonari Fujimori","orcid":"0000-0003-2142-0701","position":1,"is_corresponding":false},{"id":785018,"name":"Xiuping Fu","orcid":"0000-0002-8699-9518","position":2,"is_corresponding":false},{"id":781754,"name":"Aparna Shah","orcid":"0000-0002-7645-0775","position":3,"is_corresponding":false},{"id":684952,"name":"Atsushi Yamaguchi","orcid":"0000-0003-3776-2394","position":4,"is_corresponding":false},{"id":235990,"name":"Charles Steenbergen","orcid":"0000-0001-6654-325X","position":5,"is_corresponding":false},{"id":672734,"name":"Lakshmi Santhanam","orcid":"0000-0002-2097-9397","position":6,"is_corresponding":false},{"id":493726,"name":"Dan E. Berkowitz","orcid":"0000-0003-2232-9416","position":7,"is_corresponding":false},{"id":800765,"name":"Eric Tuday","orcid":"0000-0002-1328-5178","position":8,"is_corresponding":false},{"id":376728,"name":"Jay M. Baraban","orcid":"0000-0002-8165-2638","position":9,"is_corresponding":false},{"id":381516,"name":"Samarjit Das","orcid":"0000-0002-4377-2823","position":10,"is_corresponding":false},{"id":684950,"name":"Kei Akiyoshi","orcid":"0000-0002-3720-3341","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:36.370283Z","pmid":"37421280","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}