Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2

Huanji Zhang, Tong Wang, Kun Zhang, Yu Liu, Feifei Huang, Xinhong Zhu, Yang Liu, Mong-Heng Wang, Wanchun Tang, Jingfeng Wang, Hui Huang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. Design: Prospective, controlled, and randomized animal study. Setting: University laboratory. Subjects: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. Interventions: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. Measurements and Main Results: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2. Conclusions: Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.

Original languageEnglish (US)
Pages (from-to)e345-e354
JournalCritical care medicine
Volume42
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • cardiac fibroblast
  • cardiac hypertrophy
  • fibroblast growth factor-2
  • soluble epoxide hydrolase

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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