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

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 resultsMale 8- to10-wk-old wild-type and 5 adenosine monophosphate-activated protein kinase (AMPK)-2 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- and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Moreover, AMPK-2 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- signaling. I3C is a potential therapeutic drug for heart failure.