{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:30:25Z","timestamp":1791127825819,"version":"4.1.0"},"reference-count":61,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p> Aldosterone (Aldo) is recognized as an important risk factor for cardiovascular diseases. IL-18 induces myocardial hypertrophy, loss of contractility of cardiomyocytes, and apoptosis leading myocardial dysfunction. However, so far, there have been few reports concerning the interaction between Aldo and IL-18. The present study examined the effects and mechanisms of Aldo on IL-18 expression and the roles of peroxisome proliferator-activated receptor (PPAR) agonists in rat cardiomyocytes. We used cultured rat neonatal cardiomyocytes stimulated with Aldo to measure IL-18 mRNA and protein expression, Rho-kinase, and NF-\u03baB activity. We also investigated the effects of PPAR agonists on these actions. Aldo, endothelin-1 (ET-1), and angiotensin II (ANG II) increased IL-18 mRNA and protein expression. Mineralocorticoid receptor antagonists, endothelin A receptor antagonist, and ANG II receptor antagonist inhibited Aldo-induced IL-18 expression. Aldo induced ET-1 and ANG II production in cultured media. Moreover, Rho\/Rho-kinase inhibitor and statin inhibited Aldo-induced IL-18 expression. On the other hand, Aldo upregulated the activities of Rho-kinase and NF-\u03baB. PPAR agonists attenuated the Aldo-induced IL-18 expression and NF-\u03baB activity but not the Rho-kinase activity. Our findings indicate that Aldo induces IL-18 expression through a mechanism that involves, at a minimum, ET-1 and ANG II acting via the Rho\/Rho-kinase and PPAR\/NF-\u03baB pathway. The induction of IL-18 in cardiomyocytes by Aldo, ET-1, and ANG II might, therefore, cause a deterioration of the cardiac function in an autocrine and paracrine fashion. The inhibition of the IL-18 expression by PPAR agonists might be one of the mechanisms whereby the beneficial cardiovascular effects are exerted. <\/jats:p>","DOI":"10.1152\/ajpheart.00148.2008","type":"journal-article","created":{"date-parts":[[2008,7,25]],"date-time":"2008-07-25T21:09:33Z","timestamp":1217020173000},"page":"H1279-H1287","source":"Crossref","is-referenced-by-count":33,"title":["Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho\/Rho-kinase, and PPARs in cardiomyocytes"],"prefix":"10.1152","volume":"295","author":[{"given":"Takashi","family":"Doi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Sakoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Akagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Naka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitomo","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsujino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Masuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsumasa","family":"Ohyanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704103361506"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.23.2828"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000216039.75913.9e"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00383.2004"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00496-0"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411787200"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/hc4401.098515"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.029"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Delerive P, De Bosscher K, Vanden Berghe W, Fruchart JC, Haegeman G, Staels B. 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