Abstract | AIMS: METHODS AND RESULTS:
Fgf21 treatment in cardiomyocytes in culture induced the expression of genes encoding proteins involved in antioxidative pathways, including mitochondrial uncoupling proteins (Ucp2 and Ucp3) and superoxide dismutase-2 (Sod2) and reduced ROS production. In keeping with this, expression of antioxidant genes in response to lipopolysaccharide (LPS)-induced stimulation of pro-inflammatory pathways or isoproterenol-induced cardiac hypertrophy in the heart was reduced in Fgf21-null mice. Moreover, we found that Fgf21 is expressed in and released by cardiomyocytes in response to LPS, and its expression is under the control of the Sirt1 (sirtuin-1) pathway. This Fgf21 released by cardiomyocytes acts in an autocrine manner to protect cells against oxidative stress. Finally, failing human hearts showed up-regulation of Fgf21, Ucp3, and Sod2, confirming the association between Fgf21 induction and the control of cardiac oxidative stress pathways. CONCLUSION: Our data indicate that Fgf21 regulates genes involved in antioxidant pathways in an autocrine manner, thus preventing ROS production in cardiac cells. Therefore, Fgf21 acts as an antioxidant factor in the heart, preventing induction of pro-oxidative pathways by inflammatory or hypertrophic conditions.
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Authors | Anna Planavila, Ibon Redondo-Angulo, Francesc Ribas, Gloria Garrabou, Jordi Casademont, Marta Giralt, Francesc Villarroya |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 106
Issue 1
Pg. 19-31
(Apr 01 2015)
ISSN: 1755-3245 [Electronic] England |
PMID | 25538153
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected]. |
Chemical References |
- Ion Channels
- Lipopolysaccharides
- Mitochondrial Proteins
- Reactive Oxygen Species
- UCP2 protein, human
- UCP3 protein, human
- Ucp2 protein, mouse
- Ucp3 protein, mouse
- Uncoupling Protein 2
- Uncoupling Protein 3
- fibroblast growth factor 21
- Fibroblast Growth Factors
- Superoxide Dismutase
- superoxide dismutase 2
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Topics |
- Animals
- Autocrine Communication
(drug effects, physiology)
- Cells, Cultured
- Disease Models, Animal
- Fibroblast Growth Factors
(deficiency, pharmacology, physiology)
- Heart
(drug effects, physiology)
- Heart Failure
(metabolism, physiopathology, prevention & control)
- Humans
- Ion Channels
(physiology)
- Lipopolysaccharides
(pharmacology)
- Male
- Mice
- Mice, Knockout
- Mitochondrial Proteins
(physiology)
- Myocytes, Cardiac
(drug effects, physiology)
- Oxidative Stress
(drug effects, physiology)
- Reactive Oxygen Species
(metabolism)
- Superoxide Dismutase
(physiology)
- Uncoupling Protein 2
- Uncoupling Protein 3
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