Atorvastatin improves peroxisome proliferator-activated receptor signaling in cardiac hypertrophy by preventing nuclear factor-kappa B activation.
Nuclear factor (NF)-kappa B signaling pathway plays a pivotal role in cardiac hypertrophy. Although it has been reported that statins inhibit cardiac hypertrophy by reducing generation of reactive oxygen species, it is not yet known whether statins prevent NF-kappa B activation and whether this effect can be related to the reduction in the peroxisome proliferator-activated receptor (PPAR) pathway. In this study, we examined the role of atorvastatin on NF-kappa B activity and PPAR signaling in pressure overload-induced cardiac hypertrophy. Our findings indicate that atorvastatin inhibits cardiac hypertrophy and prevents the fall in the protein levels of PPAR alpha and PPAR beta/delta. Further, atorvastatin treatment avoided NF-kappa B activation during cardiac hypertrophy, reducing the protein-protein association between these PPAR subtypes and the p65 subunit of NF-kappa B. These findings indicate that negative cross-talk between NF-kappa B and PPARs may interfere with the transactivation capacity of the latter, leading to a fall in the expression of genes involved in fatty acid metabolism, and that these changes are prevented by statin treatment.
Planavila
Anna
A
Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain.
Laguna
Juan C
JC
Vázquez-Carrera
Manuel
M
D000818:Animals; D000069059:Atorvastatin; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006538:Heptanoic Acids / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D011312:Pressure; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D021122:Protein Subunits; D011758:Pyrroles; D000069059:Atorvastatin