{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:50:55Z","timestamp":1788292255502,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["SFB Transregio TRR-267"],"award-info":[{"award-number":["SFB Transregio TRR-267"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: A deregulated aldosterone (Aldo)\u2013mineralocorticoid receptor (MR) pathway is linked to cardiovascular disease (CVD), including hypertension and heart failure. Despite the association of elevated plasma Aldo levels with cardiac stress, inflammation, myocardial fibrosis, and cardiac remodeling, the underlying mechanisms remain elusive. Methods: To study the impact of Aldo\u2013MR pathway overactivation on cardiac health, a novel mouse model with AAV9-mediated MR overexpression and Aldo administration via subcutaneous osmotic pumps was generated. Echocardiographic analyses, transcriptome sequencing, and loss-of-function experiments of an identified lead candidate gene were performed. Additionally, cardiac tissue samples from human patients with end-stage heart failure were analyzed in the study. Results: Mice with an overactivated Aldo\u2013MR pathway exhibited increased neutrophil gelatinase-associated lipocalin (NGAL) expression, cardiac dysfunction, hypertrophy, and fibrosis. Transcriptomics identified prostaglandin D2 synthase (Ptgds) as a novel downstream effector of the cardiac Aldo\u2013MR pathway. SiRNA-mediated inhibition of Ptgds in primary cardiomyocytes reduced NGAL levels and the hypertrophic impact of Aldo, suggesting a role in mediating Aldo-induced cardiac pathologies. Elevated expression of PTGDS was observed in hiPSC-CMs treated with the pro-hypertrophic cytokine leukemia inhibitory factor (LIF) and in end-stage heart failure patients, ascertaining its importance in cardiac disease settings. Conclusions: PTGDS is a newly identified mediator of Aldo\u2013MR-induced cardiac remodeling and may represent a potential therapeutic target for CVD.<\/jats:p>","DOI":"10.3390\/cells14191485","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:48:37Z","timestamp":1758635317000},"page":"1485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prostaglandin D2 Synthase: A Novel Player in the Pathological Signaling Mechanism of the Aldosterone\u2013Mineralocorticoid Receptor Pathway in the Heart"],"prefix":"10.3390","volume":"14","author":[{"given":"Ankita","family":"Garg","sequence":"first","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Juchem","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"},{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 30625 Hannover, 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, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2337-1034","authenticated-orcid":false,"given":"Carla Nunes","family":"Borisch","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6140-2116","authenticated-orcid":false,"given":"Julia","family":"Leonardy","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-9383","authenticated-orcid":false,"given":"Christian","family":"B\u00e4r","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"},{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 30625 Hannover, Germany"},{"name":"Fraunhofer Cluster of Excellence Immune-Mediated Diseases (CIMD), 30625 Hannover, 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, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-1511","authenticated-orcid":false,"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics\u20142020 Update a Report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/ajh\/hpy120","article-title":"Mineralocorticoid Receptor and Cardiovascular Disease","volume":"31","author":"Buonafine","year":"2018","journal-title":"Am. 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