Source:http://linkedlifedata.com/resource/pubmed/id/18660453
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-9-8
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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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
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0363-6135
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
295
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H1279-H1287
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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
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pubmed:year |
2008
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pubmed:articleTitle |
Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes.
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pubmed:affiliation |
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya-City, Hyogo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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