Fat-free diet for the heart
Changes in the nutrition of heart cells can help them recover
A new study suggests that stimulating cardiomyocytes to consume glucose instead of fatty acids may help in the treatment of heart failure, according to a press release from UT Southwestern Changing what heart cells eat could help them regenerate.
Article by Cardoso et al. Mitochondrial substrate utilization regulates cardiomyocyte cell-cycle progression published in the journal Nature Metabolism – VM.
If you change the way heart cells are fed, you can find new ways to treat various conditions in which the heart muscle is damaged, including heart failure caused by viruses, toxins, high blood pressure or a heart attack.
Current pharmaceutical treatments for heart failure, including ACE inhibitors and beta-blockers, are aimed at stopping the destruction of the heart muscle, since tension further damages it, causing the death of more cells," explains Hesham A. Sadek, a researcher at the University of Texas Southwestern Medical Center in Dallas. There are no treatments available to repair the heart muscle.
Nine years ago, Sadek and his colleagues discovered that mammalian hearts can regenerate with the help of cardiomyocytes – cells responsible for the contractile force of the heart, if the damage occurred in the first few days of life. However, by 7 days of life, this ability is completely lost, which is a sharp turning point at which the division of these cells slows down dramatically. Subsequent studies have shown that this change in regenerative capacity appears to occur, at least in part, from damage to free radicals generated by organelles known as mitochondria, which nourish cells. These free radicals damage the DNA of cells, which prompts them to stop dividing.
Sadek explains that the shift in free radical production is caused by a change in what mitochondria in cardiomyocytes use for energy. In the womb and at birth, mitochondria rely on glucose, and a few days after birth they switch to fatty acids to use these energy-rich molecules in breast milk.
Sadek and his colleagues wondered if forcing mitochondria to continue consuming glucose could block DNA damage and, in turn, expand the window for heart cell regeneration. To test this idea, the researchers conducted two different experiments.
In the first case, they examined baby mice whose mothers had been genetically modified so that their milk had a low fat content, then these mice were given a low fat feed. The researchers found that the hearts of these rodents retained the ability to regenerate a few weeks later than usual, while their cardiomyocytes continued to express genes associated with cell division for a significantly longer period of time than those who ate regular milk and food. However, this effect did not last into adulthood – their liver eventually made up for the deficiency by synthesizing fats that were absent from their diet, which significantly reduced the regenerative capacity of their hearts.
In the second experiment, the researchers created genetically modified animals in which scientists could remove an enzyme known as pyruvate dehydrogenase kinase 4 (PDK4), necessary for the mitochondria of heart cells to digest fatty acids. When the researchers delivered the drug to turn off PDK4 production, the animals' cardiomyocytes switched to glucose consumption instead of fatty acids, even in adulthood. After the researchers simulated a heart attack, these animals showed an improvement in heart function, which was accompanied by markers in gene expression, suggesting that their cardiomyocytes were still actively dividing.
Sadek notes that these results are proof of the principle that it is possible to open a window for the regeneration of heart cells by manipulating what the mitochondria of cardiomyocytes consume for energy.
"Eventually," he says, "it may be possible to develop drugs that change what cardiomyocytes consume to make them divide again, reversing heart failure..."
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