{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:55:33Z","timestamp":1770069333026,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T00:00:00Z","timestamp":1166572800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Inhibitors of 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A reductase (statins) manifest pleiotropic effects that may contribute to their therapeutic efficacy. However, the mechanism of the beneficial action of statins on cardiac hypertrophy and fibrosis remains unclear. We have now investigated this action of pitavastatin in Dahl salt\u2010sensitive (DS) rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The DS rats progressively develop marked hypertension when fed a diet containing 8% NaCl from 7 weeks of age. These animals exhibited pronounced cardiac hypertrophy and fibrosis, as well as upregulation of fetal\u2010type cardiac gene expression at 12 weeks of age, compared with DS rats fed a diet containing 0.3% NaCl. The abundance of mRNAs for collagen types I and III, angiotensin\u2010converting enzyme, transforming growth factor\u2010\u03b21 and connective tissue growth factor was also increased in the heart of rats on the high\u2010salt diet.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Treatment of rats on the high\u2010salt diet with a non\u2010antihypertensive dose of pitavastatin (0.3 or 1\u00a0mg\/kg per day) from 7 to 12 weeks of age attenuated the development of cardiac hypertrophy and fibrosis, as well as inhibiting the upregulation of cardiac gene expression. Pitavastatin also blocked the translocation of RhoA to the membrane fraction of the left ventricle and RhoA activation, as well as the phosphorylation of the mitogen\u2010activated protein kinases extracellular signal\u2010regulated kinase (ERK)\u20101 and ERK\u20102 and an increase in the DNA binding activity of serum response factor (SRF) in the heart induced by the high\u2010salt diet.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings suggest that the effects of pitavastatin on load\u2010induced cardiac hypertrophy and fibrosis are independent of its cholesterol\u2010lowering action and may be mediated, at least in part, through inhibition of RhoA\u2013ERK\u2013SRF signalling.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/j.1440-1681.2006.04508.x","type":"journal-article","created":{"date-parts":[[2006,12,21]],"date-time":"2006-12-21T06:06:14Z","timestamp":1166681174000},"page":"1164-1171","source":"Crossref","is-referenced-by-count":26,"title":["ATTENUATION OF VENTRICULAR HYPERTROPHY AND FIBROSIS IN RATS BY PITAVASTATIN: POTENTIAL ROLE OF THE RhoA\u2013EXTRACELLULAR SIGNAL\u2010REGULATED KINASE\u2013SERUM RESPONSE FACTOR SIGNALLING PATHWAY"],"prefix":"10.1111","volume":"33","author":[{"given":"Masako","family":"Saka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Obata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahoko","family":"Ichihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian Wu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Kimata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Noda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Izawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohzo","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,12,20]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01360-2"},{"key":"e_1_2_5_3_2","first-page":"639","article-title":"Is there major involvement of the renin\u2013angiotensin system in cardiac hypertrophy?","volume":"81","author":"Yamazaki T","year":"1997","journal-title":"Circ. 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