{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:20:30Z","timestamp":1790256030421,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aldosterone\u2013mineralocorticoid receptor (Aldo\u2013MR) pathway is activated during cardiac stress, such as hypertension, myocardial infarction (MI), and heart failure. The importance of Aldo and MR in the pathogenesis of cardiac diseases is well established; however, the regulatory mechanisms behind Aldo\/MR-induced cardiac remodelling remain uncertain. We here investigated potential miRNA-mediated regulation of the Aldo\u2013MR pathway to improve mechanistic understanding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>High-throughput screening of 2,555 miRNAs using an MR responsive stable cardiomyocyte cell line (MMTV-GFP-HL-1) identified miR-181a as a potential regulator of Aldo\u2013MR pathway. MiR-181a was found to downregulate the expression of Ngal (lipocalin-2), a well-established downstream effector molecule of Aldo\u2013MR. In addition, Aldo-induced cellular hypertrophy decreased significantly upon miR-181a overexpression. Genetic miR-181 knockout in murine MI model led to deteriorated cardiac function, cardiac remodelling, and activation of Aldo\u2013MR pathway while AAV9-mediated miR-181a overexpression improved cardiac function and deactivated Aldo\u2013MR pathway proving a cardio-protective role of miR-181a. Global RNA sequencing of cells under Aldo treatment with\/without miR-181a overexpression identified potential miR-181a targets functionally contributing to Aldo\u2013MR pathway. Adamts1, a direct target of miR-181a, was found to be downregulated with miR-181a overexpression and upregulated with inhibition. Similar to miR-181a overexpression, siRNA-mediated inhibition of Adamts1 inhibited Aldo\u2013MR pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We here show that miR-181a is a novel regulator of the Aldo\u2013MR pathway regulating the levels of Ngal via direct targeting of Adamts1. This new insight establishes miR-181a as a factor of immense value participating in downstream networks of Aldo\u2013MR pathway. Our in vivo studies further confirmed miR-181a as cardio-protective under MI stress. Thus, miR-181a\u2019s involvement in Aldo\u2013MR-mediated cardiac remodelling confers it with tremendous potential to be developed further as a new therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1813","type":"journal-article","created":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T16:14:48Z","timestamp":1587226488000},"page":"1366-1377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["MiRNA-181a is a Novel Regulator of Aldosterone\u2013Mineralocorticoid Receptor-Mediated Cardiac Remodelling"],"prefix":"10.1093","volume":"22","author":[{"given":"Ankita","family":"Garg","sequence":"first","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Foinquinos","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Janssen-Peters","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinje","family":"Biss","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]},{"name":"Council of Scientific and Industrial Research - Central Drug Research Institute , Lucknow ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Hannover ,","place":["Germany"]},{"name":"REBIRTH Center of Translational Regenerative Medicine, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,18]]},"reference":[{"key":"2026011721364820400_ejhf1813-bib-0001","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0735-1097(99)00630-0","article-title":"Cardiac remodeling \u2013 concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. 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