{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:25:21Z","timestamp":1760149521526,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodeling. In this context, we aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor beta-1 (TGF-\u03b21) in an in vivo model. Six-week-old male wild-type (WT) and TGF-\u03b21-overexpressing transgenic (TGF-\u03b21-TG) mice were infused with subhypertensive doses of Ald for 2 weeks and\/or treated orally with eplerenone from postnatal day 21. Thehearts\u2019 ventricles were examined by morphometry, immunoblotting to assess the intracellular signaling pathways and RT qPCR to determine hypertrophy and fibrosis marker genes. The TGF-\u03b21-TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis and exhibited a higher baseline phosphorylation of p44\/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in the ventricular-heart-weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but a less pronounced increase in interstitial fibrosis in the transgenic compared to the WT mice (23.6% vs. 80.9%, p &lt; 0.005). Ald increased the phosphorylation of p44\/42 and p38 in the WT but not the TGF-\u03b21-TG mice. While the eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in the WT controls, it completely protected against additional fibrosis in transgenic mice. Ald appears to induce cardiac hypertrophy independently of TGF-\u03b21, while in the case of fibrosis, the downstream signaling pathways of these two factors probably converge.<\/jats:p>","DOI":"10.3390\/ijms241512237","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T09:22:38Z","timestamp":1690795358000},"page":"12237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Role of Aldosterone and Transforming Growth Factor Beta-1 in Cardiac Remodeling"],"prefix":"10.3390","volume":"24","author":[{"given":"Piotr","family":"Kmie\u0107","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Medical University of Gda\u0144sk, 80214 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine III and Cologne Cardiovascular Research Center, Cologne University Heart Center, 50937 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2424-0960","authenticated-orcid":false,"given":"Margarete","family":"Odenthal","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital of Cologne and Center for Molecular Medicine, University of Cologne, 50937 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5707-8285","authenticated-orcid":false,"given":"Evren","family":"Caglayan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University-Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and Pathological Cardiac Hypertrophy","volume":"97","author":"Shimizu","year":"2016","journal-title":"J. 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