Indole-3-carbinol protects against pressure overload induced cardiac remodeling via activating AMPK-α.

Abstract

SCOPE:

Indole-3-carbinol (I3C), a monomer component extracted from leaves and stems of cruciferous vegetables, has inhibitory effects on tumors, obesity, and liver fibrosis, but its effects on the development of cardiac remodeling remain completely unknown. We determined the effects of I3C on cardiac remodeling and heart function using an aortic banding (AB) mouse model.

METHODS AND RESULTS:

Male 8- to10-wk-old wild-type and 5' adenosine monophosphate-activated protein kinase (AMPK)-α2 knockout mice fed with or without I3C were subjected to AB or a sham operation and were phenotyped, accordingly. I3C both prevented and reversed cardiac remodeling induced by AB, as assessed by heart weight/body weight, lung weight/body weight, and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. The inhibitory effect of I3C on cardiac remodeling was mediated by AMPK-α and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Moreover, AMPK-α2 gene deficiency completely blocked the inhibitory effects of I3C on cardiac remodeling, preventing the improvements in heart weight/body weight, lung weight/body weight, heart weight/tibia length, cardiac function, gene expression of hypertrophic and fibrotic markers, and phosphorylation of mammalian target of rapamycin and ERK1/2 signaling components.

CONCLUSION:

I3C both prevents and reverses cardiac remodeling by activating AMPK-α signaling. I3C is a potential therapeutic drug for heart failure.

• Authors: Wei Deng, Jing Zong, Zhouyan Bian, Heng Zhou, Yuan Yuan, Rui Zhang, Haipeng Guo, Yan Zhang, Difei Shen, Hongliang Li, Qizhu Tang
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 57 Issue 9 Pg. 1680-7 (Sep 2013) ISSN: 1613-4133 [Electronic] Germany
• PMID: 23625645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Indoles
• Plant Extracts
• indole-3-carbinol
• mTOR protein, mouse
• AMPK alpha2 subunit, mouse
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Animals
• Body Weight
• Cardiomegaly (drug therapy, pathology, prevention & control)
• Fibrosis
• Heart (drug effects, physiopathology)
• Indoles (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Organ Size (drug effects)
• Phosphorylation
• Plant Extracts (pharmacology)
• Pressure (adverse effects)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Vegetables (chemistry)