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Atorvastatin improves peroxisome proliferator-activated receptor signaling in cardiac hypertrophy by preventing

Anna Planavila1, Juan C Laguna, Manuel Vázquez-Carrera

  • 1Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain.

Biochimica Et Biophysica Acta
|February 15, 2005
PubMed

Insights

Atorvastatin prevents cardiac hypertrophy by inhibiting Nuclear Factor-kappa B (NF-kappa B) activation. This statin treatment preserves peroxisome proliferator-activated receptor (PPAR) signaling, crucial for fatty acid metabolism.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pharmacology

Background:

  • Nuclear Factor-kappa B (NF-kappa B) signaling is critical in cardiac hypertrophy.
  • Statins are known to reduce reactive oxygen species, but their effect on NF-kappa B activation and peroxisome proliferator-activated receptor (PPAR) pathways in cardiac hypertrophy is unclear.

Purpose of the Study:

  • To investigate the role of atorvastatin in modulating NF-kappa B activity and PPAR signaling during pressure overload-induced cardiac hypertrophy.
  • To determine if statin-mediated inhibition of cardiac hypertrophy is linked to effects on the PPAR pathway.

Main Methods:

  • Utilized a model of pressure overload-induced cardiac hypertrophy.
  • Assessed the impact of atorvastatin on NF-kappa B activation.
  • Quantified protein levels of PPAR alpha and PPAR beta/delta.
  • Examined protein-protein interactions between PPAR subtypes and the p65 subunit of NF-kappa B.

Main Results:

  • Atorvastatin effectively inhibited cardiac hypertrophy.
  • Treatment with atorvastatin prevented the decrease in protein levels of PPAR alpha and PPAR beta/delta.
  • Atorvastatin administration blocked NF-kappa B activation and reduced interactions between PPARs and NF-kappa B p65 subunit.

Conclusions:

  • Negative cross-talk between NF-kappa B and PPARs contributes to cardiac hypertrophy by impairing fatty acid metabolism gene expression.
  • Atorvastatin treatment prevents these detrimental changes, suggesting a novel mechanism for statin action in cardiac hypertrophy.

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