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Fasudil alleviates pressure overload-induced heart failure by activating Nrf2-mediated antioxidant responses

Peng Guan1,2, Yingran Liang1, Na Wang1

  • 1School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.

Journal of Cellular Biochemistry
|January 12, 2018
PubMed

Insights

Fasudil, a Rho-kinase inhibitor, protects against pressure overload heart failure in rats by enhancing antioxidant activity and activating the Nrf2 pathway. This suggests fasudil as a potential treatment for heart failure.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Molecular Biology

Background:

  • The RhoA/Rho-kinase pathway is crucial for cardiovascular function.
  • Pressure overload leads to heart failure, a significant clinical challenge.
  • Identifying effective therapeutic targets for heart failure is essential.

Purpose of the Study:

  • To investigate the protective effects of fasudil, a Rho-kinase inhibitor, against pressure overload-induced heart failure in rats.
  • To elucidate the underlying mechanisms of fasudil's protective action, focusing on oxidative stress and the Nrf2 pathway.

Main Methods:

  • Heart failure was induced in Sprague-Dawley rats via abdominal aortic banding for 8 weeks.
  • Rats were treated with varying doses of fasudil (5 and 10 mg/kg/day) or vehicle.
  • Echocardiography, transmission electron microscopy, and biochemical assays were used for evaluation.

Main Results:

  • Fasudil significantly inhibited the progression of heart failure, improving cardiac function.
  • Fasudil dose-dependently increased antioxidant enzyme activities (SOD, CAT, GPx) and decreased lipid peroxidation (MDA).
  • Fasudil promoted nuclear translocation of Nrf2, enhancing antioxidant gene expression and increasing iron and TfR1 levels.

Conclusions:

  • Fasudil exerts protective effects against pressure overload-induced heart failure in rats.
  • These protective effects are attributed to enhanced antioxidative activities mediated by the Nrf2 pathway.
  • Fasudil represents a promising therapeutic strategy for heart failure, offering a novel treatment concept.
Keywords:
Nrf2fasudilheart failureironoxidative stress

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