Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-9-8
pubmed:abstractText
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-kappaB 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-kappaB. PPAR agonists attenuated the Aldo-induced IL-18 expression and NF-kappaB 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-kappaB 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Aldosterone, http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/BQ 788, http://linkedlifedata.com/resource/pubmed/chemical/Bezafibrate, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers, http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Peroxisome Proliferator-Activated..., http://linkedlifedata.com/resource/pubmed/chemical/Piperidines, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/cyclo(Trp-Asp-Pro-Val-Leu), http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1279-H1287
pubmed:meshHeading
pubmed-meshheading:18660453-Aldosterone, pubmed-meshheading:18660453-Angiotensin II, pubmed-meshheading:18660453-Animals, pubmed-meshheading:18660453-Animals, Newborn, pubmed-meshheading:18660453-Bezafibrate, pubmed-meshheading:18660453-Cells, Cultured, pubmed-meshheading:18660453-DNA Primers, pubmed-meshheading:18660453-Dose-Response Relationship, Drug, pubmed-meshheading:18660453-Endothelin-1, pubmed-meshheading:18660453-Interleukin-18, pubmed-meshheading:18660453-Myocytes, Cardiac, pubmed-meshheading:18660453-NF-kappa B, pubmed-meshheading:18660453-Oligopeptides, pubmed-meshheading:18660453-Peptides, Cyclic, pubmed-meshheading:18660453-Peroxisome Proliferator-Activated Receptors, pubmed-meshheading:18660453-Piperidines, pubmed-meshheading:18660453-Rats, pubmed-meshheading:18660453-Rats, Sprague-Dawley, pubmed-meshheading:18660453-Thiazolidinediones, pubmed-meshheading:18660453-rho-Associated Kinases
pubmed:year
2008
pubmed:articleTitle
Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes.
pubmed:affiliation
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya-City, Hyogo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't