Soy diet worsens heart disease in mice

Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Journal of Clinical Investigation (Impact Factor: 13.22). 02/2006; 116(1):209-16. DOI: 10.1172/JCI24676
Source: PubMed


We report that dietary modification from a soy-based diet to a casein-based diet radically improves disease indicators and cardiac function in a transgenic mouse model of hypertrophic cardiomyopathy. On a soy diet, males with a mutation in the alpha-myosin heavy chain gene progress to dilation and heart failure. However, males fed a casein diet no longer deteriorate to severe, dilated cardiomyopathy. Remarkably, their LV size and contractile function are preserved. Further, this diet prevents a number of pathologic indicators in males, including fibrosis, induction of beta-myosin heavy chain, inactivation of glycogen synthase kinase 3beta (GSK3beta), and caspase-3 activation.

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Available from: John P Konhilas, Dec 23, 2013
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    • "To identify putative AMPK-target specific miRs, we performed a real-time PCR screen using the R403Q transgenic mouse model of HCM to identify disease-associated miRs [22], [23]. R403Q HCM mice express a mutant myosin heavy chain (R403Q) corresponding to a human mutation causing HCM and possess multiple phenotypic similarities with their human counterparts [22], [24]. More importantly, this R403Q model also demonstrates the energetic abnormalities that occur in cardiac disease states [25], [26]. "
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    ABSTRACT: Recently, MicroRNAs (miR) and AMP-kinase (AMPK) have emerged as prominent players in the development of cardiac hypertrophy and heart failure. We hypothesized that components of the adenosine monophosphate-activated kinase (AMPK) pathway are targeted by miRs and alter AMPK signaling during pathological cardiac stress. Using a mouse model of hypertrophic cardiomyopathy (HCM), we demonstrated early elevation of miR-195 and miR-451 in HCM hearts, which targets MO25, a central component of the MO25/STRAD/LKB1 complex that acts as an upstream kinase for AMPK. We show functional targeting of MO25 by miR-195 and -451. Further in vitro interrogation of MO25 as a functional target validated this hypothesis where over-expression of miR-195 in C2C12 cells knocked down MO25 expression levels and downstream AMPK signaling (phosphorylation of Acetyl CoA carboxylase [ACC] and AMPK activity assay), similar to MO25 knockdown in C2C12 cells by siRNA. Parallel changes were measured in 60 day R403Q HCM male hearts that were rescued by short-term administration of AICAR, an AMPK agonist. Elevated miR-195 targets the LKB1/AMPK signaling axis in HCM progression and implicates a functional role in HCM disease progression. MiR-195 may serve as potential therapeutics or therapeutic targets for heart disease.
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    • "We have studied sex dimorphisms in R403Q mice and characterized some of the cellular and molecular mechanisms behind the sex differences [43] [92]. These include a number of pathologic indicators such as fibrosis, induction of β-myosin heavy chain, inactivation of glycogen synthase kinase-3β, and activation of proapoptotic pathways in males but not females [43] [92] [94]. Males harboring the R403Q mutation show progressive deterioration in ventricular function associated with chamber dilation whereas females R403Q mice do not [92] [95] [96]. "
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    BioMed Research International 04/2010; 2010(1110-7243):562051. DOI:10.1155/2010/562051 · 2.71 Impact Factor
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    • "Water—Diet can have a dramatic and rapid impact on cellular responses and gene expression, as illustrated by effects of soy or casein on cardiac hypertrophy (Stauffer et al., 2006) and how a diet enriched with omega-3 fatty acids can have potent post-natal effects on fetal programming (Wyrwoll et al., 2006): both of these studies emphasise the strong influence of gender. There is a huge literature on nutritional effects but these two examples illustrate the need for strictly standardised diets. "
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