{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T05:33:51Z","timestamp":1740116031141,"version":"3.37.3"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/16\/12\/32451"],"award-info":[{"award-number":["RG\/16\/12\/32451"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>A reduction in both dystrophin and neuronal nitric oxide synthase (NOS1) secondary to microRNA-31 (miR-31) up-regulation contributes to the atrial electrical remodelling that underpins human and experimental atrial fibrillation (AF). In contrast, patients with Duchenne muscular dystrophy (DMD), who lack dystrophin and NOS1 and, at least in the skeletal muscle, have raised miR-31 expression, do not have increase susceptibility to AF in the absence of left ventricular (LV) dysfunction. Here, we investigated whether dystrophin deficiency is also associated with atrial up-regulation of miR-31, loss of NOS1 protein, and increased AF susceptibility in young mdx mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Echocardiography showed normal cardiac structure and function in 12\u201313 weeks mdx mice, with no indication by assay of hydroxyproline that atrial fibrosis had developed. The absence of dystrophin in mdx mice was accompanied by an overall reduction in syntrophin and a lower NOS1 protein content in the skeletal muscle and in the left atrial and ventricular myocardium, with the latter occurring alongside reduced Nos1 transcript levels (exons 1\u20132 by quantitative polymerase chain reaction) and an increase in NOS1 polyubiquitination [assessed using tandem polyubiquitination pulldowns; P &amp;lt; 0.05 vs. wild type (WT)]. Neither the up-regulation of miR-31 nor the substantial reduction in NOS activity observed in the skeletal muscle was present in the atrial tissue of mdx mice. At difference with the skeletal muscle, the mdx atrial myocardium showed a reduction in the constitutive NOS inhibitor, caveolin-1, coupled with an increase in NOS3 serine1177 phosphorylation, in the absence of differences in the protein content of other NOS isoforms or in the relative expression NOS1 splice variants. In line with these findings, transoesophageal atrial burst pacing revealed no difference in AF susceptibility between mdx mice and their WT littermates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Dystrophin depletion is not associated with atrial miR-31 up-regulation, reduced NOS activity, or increased AF susceptibility in the mdx mouse. Compared with the skeletal muscle, the milder atrial biochemical phenotype may explain why patients with DMD do not exhibit a higher prevalence of atrial arrhythmias despite a reduction in NOS1 content.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae022","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T17:18:57Z","timestamp":1706203137000},"page":"519-530","source":"Crossref","is-referenced-by-count":1,"title":["Why is early-onset atrial fibrillation uncommon in patients with Duchenne muscular dystrophy? Insights from the <i>mdx<\/i> mouse"],"prefix":"10.1093","volume":"120","author":[{"given":"My-Nhan","family":"Nguyen","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Hooper","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matilde","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Besarte","family":"Vrellaku","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7440-2964","authenticated-orcid":false,"given":"Ricardo","family":"Carnicer","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Muscular Dystrophy UK Oxford Neuromuscular Centre, University of Oxford , Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian N","family":"Simon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-1617","authenticated-orcid":false,"given":"Barbara","family":"Casadei","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , L6 West Wing, Oxford OX3 9DU , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"2024043016362385100_cvae022-B1","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1161\/CIRCULATIONAHA.114.015151","article-title":"Contemporary cardiac issues in Duchenne muscular dystrophy. 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