This is the first study to provide evidence that an environmental influence - in this case diet - can affect the heart. It will also force researchers to rethink the diets of their laboratory mice. The results appear in the Journal of Clinical Investigation.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease occurring in 1 in 500 individuals, and is characterized by shortness of breath, chest discomfort, and palpitations that may be a sign of life-threatening arrhythmias. While mutations in a number of genes have been linked to HCM, the variety of symptoms experienced by sufferers suggests that other genetic or environmental factors affect disease prognosis.
For years, soy-rich diets have been speculated to protect against heart disease. The biological consequences of a soy-diet have been attributed to the presence of phytoestrogens, which are plant-derived estrogen-like compounds that interact with the estrogen receptor. Leslie Leinwand and colleagues examined male and female mice that overexpressed a mutant form of the alpha myosin heavy chain gene, which is one known cause of HCM in humans. The researchers found significant growth (known as hypertrophy) of the heart of male mice fed a soy-based diet, in comparison to male and female mutant mice fed a soy-free diet.
The authors propose that the difference observed between the sexes is based on the fact that the female mice, who are constantly exposed to naturally circulating levels of estrogen compounds, are less sensitive than males to the change in estrogen level as a result of the soy diet. Interestingly, the authors observed a significant improvement in cardiac growth and function when the animals were switched to a soy-free diet. The new data provide a strong link between soy diet and the progression of cardiac disease, in mice.
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"Currently, we don't have any targeted treatments like tamoxifen or Herceptin for the aggressive type of breast tumors that express alphaB-crystallin. Our results suggest that these tumors may respond to drugs that block this important pathway activated by alphaB-crystallin," Cryns said.
Cryns' laboratory group also observed that non-cancerous breast cells genetically manipulated to express alphaB-crystallin form aggressive breast tumors when injected into mice, confirming their malignant nature.
What's more, the team found that these mouse tumors were similar in many respects to human breast tumors which express alphaB-crystallin, suggesting that this mouse model may be useful for testing new treatments for these poor-prognosis tumors. Indeed, the researchers are currently exploring whether drug inhibitors of the MEK-ERK pathway block breast tumor growth in mice.
Collaborating with Cryns and Moyano were Torsten O. Nielson and Dmitry Turbin, University of British Columbia, Vancouver; and Charles M. Perou and Gamze Karaca, University of North Carolina at Chapel Hill. Other members of the research team at Northwestern University were Fruma Yehiely, Joseph R. Evans, Feng Chen, Meiling Lu, Michael E. Werner, Leslie Diaz and Elizabeth Wiley.
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