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Here we examined the possibility that aldosterone modulates 12\u2010 and\/or 15\u2010lipoxygenase (LO) expression\/activity in human vascular smooth muscle cells (VSMC), in vitro, thereby potentially contributing to both vascular reactivity and atherogenesis. Following 24\u2009h treatment of VSMC with aldosterone (1\u2009nmol\/L), there was a \u223c2\u2010fold increase in the generation rate of 12 hydroxyeicosatetraenoic acid (12\u2010HETE), 70% increase in platelet type 12\u2010LO mRNA expression (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) along with a \u223c3\u2010fold increase in 12\u2010LO protein expression, which were blocked by the mineralocorticoid receptor (MR) antagonists spironolactone (100\u2009nmol\/L) and eplerelone (100\u2009nmol\/ml). Additionally, aldosterone (1\u2009nmol\/L; 24\u2009h) increased the production of 15\u2010HETE (50%; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and the expression of 15\u2010LO type 2 mRNA (50%; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) (in VSMC). Aldosterone also increased the 12\u2010 and 15\u2010LO type 2 mRNA expression in a line of human aortic smooth muscle cells (T\/G HA\u2010VSMC) (60% and 50%, respectively). Aldosterone\u2010induced 12\u2010 and 15\u2010LO type 2 mRNA expressions were blocked by the EGF\u2010receptor antagonist AG 1478 and by the MAPK\u2010kinase inhibitor UO126. Aldosterone\u2010treated VSMC also showed increased LDL oxidation, (\u223c2\u2010fold; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), which was blocked by spironolactone. In conclusion, aldosterone increased 12\u2010 and 15\u2010LO expression in human VSMC, in association with increased 12\u2010 and 15\u2010HETE generation and enhanced LDL oxidation and may directly augment VSMC contractility, hypertrophy, and migration through 12\u2010HETE and promote LDL oxidation via the pro\u2010oxidative properties of these enzymes. J. Cell. Biochem. 108: 1203\u20131210, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22352","type":"journal-article","created":{"date-parts":[[2009,9,30]],"date-time":"2009-09-30T17:48:19Z","timestamp":1254332899000},"page":"1203-1210","source":"Crossref","is-referenced-by-count":21,"title":["Aldosterone up\u2010regulates 12\u2010 and 15\u2010lipoxygenase expression and LDL oxidation in human vascular smooth muscle cells"],"prefix":"10.1002","volume":"108","author":[{"given":"Rona","family":"Limor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Sharon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Knoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Naidich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Weisinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Keidar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naftali","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(01)35247-3"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23225"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1993.1066"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.174235"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1098-8823(03)00048-0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5897"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(86)90533-6"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.2.F181"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-003-0012-2"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.48.1.231"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00159.2001"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2007.07.001"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0469"},{"key":"e_1_2_5_15_1","doi-asserted-by":"crossref","first-page":"24316","DOI":"10.1016\/S0021-9258(19)51084-5","article-title":"Vascular aldosterone. 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