Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failuremodel rats

Hirokuni Akahori, Takeshi Tsujino, Yoshiro Naito, Mika Matsumoto, Naoko Sasaki, Toshihiro Iwasaku, Akiyo Eguchi, Hisashi Sawada, Shinichi Hirotani, Tohru Masuyama

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Objective: Clinical studies have suggested the beneficial effects of statin therapy on diastolic heart failure. However, the mechanism of the beneficial effects of statin on diastolic heart failure remains unknown. We examined the effect of atorvastatin on the cardiac function of Dahl salt-sensitive rat, a model of hypertensive diastolic heart failure. Methods: Dahl salt-sensitive rats were divided into three groups: the low-salt group (given standard diet), the highsalt group (given 8% NaCl diet from 7 weeks of age), and the high-saltRatorvastatin (HSRAto) group (given 8% NaCl diet from 7 weeks of age and atorvastatin from 17 weeks of age). We evaluated left ventricular hypertrophy (LVH), fibrosis, and function by using echocardiography and histology. We also examined the expression of molecules related to fibrosis in the hearts of Dahl salt-sensitive rats and cultured rat cardiac fibroblasts. Results: Left ventricular hypertrophy, diastolic dysfunction, and cardiac fibrosis were observed in the high-salt group. Atorvastatin ameliorated cardiac fibrosis and normalized left ventricular diastolic function without altering blood pressure. Atorvastatin also decreased the expression of heat shock protein 47 (HSP47), an essential chaperone for type 1 collagen processing, without changing in expression of transforming growth factor beta. In rat cardiac fibroblast cells, atorvastatin also reduced HSP47 level induced by transforming growth factor beta. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate and mimicked by Rho kinase inhibitor. Conclusion: Atorvastatin administration ameliorates cardiac fibrosis and improves left ventricular diastolic function in Dahl salt-sensitive rats. Lowering HSP47 by atorvastatin via inhibition of Rho-Rho kinase pathway is suggested as a mechanism.

Original languageEnglish
Pages (from-to)1534-1541
Number of pages8
JournalJournal of Hypertension
Volume32
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Cardiac fiblosis
  • Diastolic heart failure
  • Heat shock protein 47
  • Statin

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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