Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin: Potential role of the RhoA-extracellular signal-regulated kinase-serum response factor signalling pathway

Masako Saka, Koji Obata, Sahoko Ichihara, Xian Wu Cheng, Hirotaka Kimata, Akiko Noda, Hideo Izawa, Kohzo Nagata, Mitsuhiro Yokota

研究成果: Article査読

26 被引用数 (Scopus)

抄録

1. Inhibitors of 3-hydroxy-3-methylglutaryl 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-sensitive (DS) rats. 2. 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-type 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-converting enzyme, transforming growth factor-β1 and connective tissue growth factor was also increased in the heart of rats on the high-salt diet. 3. Treatment of rats on the high-salt diet with a non-antihypertensive dose of pitavastatin (0.3 or 1 mg/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-activated protein kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 and an increase in the DNA binding activity of serum response factor (SRF) in the heart induced by the high-salt diet. 4. These findings suggest that the effects of pitavastatin on load-induced cardiac hypertrophy and fibrosis are independent of its cholesterol-lowering action and may be mediated, at least in part, through inhibition of RhoA-ERK-SRF signalling.

本文言語English
ページ(範囲)1164-1171
ページ数8
ジャーナルClinical and Experimental Pharmacology and Physiology
33
12
DOI
出版ステータスPublished - 01-12-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生理学
  • 薬理学
  • 生理学(医学)

フィンガープリント

「Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin: Potential role of the RhoA-extracellular signal-regulated kinase-serum response factor signalling pathway」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル