Healing a broken heart

Reduced heart function due to aging and disease is a major health problem. Heart attacks can have devastating impacts, often leading to the death of the patient or chronic morbidity for those that survive.

A major reason for the sensitivity of the circulatory system to heart malfunction is that heart muscle cells (cardiomyocytes) of adult mammals generally do not divide. This means that when a cardiomyocyte dies, due to localized loss of blood supply, for example, that dead cell will never be replaced. Normally, heart tissue has a robust, healthy blood supply, but when a heart attack strikes, portions of heart tissue are deprived of blood flow, resulting in rapid cell death in those sections of the heart.

Recovering the ability to heal

Interestingly, newborn hearts can heal. In 2011, scientists discovered that newborn mice are able to regenerate cardiomyocytes to repair heart damage, but this ability is lost soon after birth¹. More recently, researchers discovered that the high-oxygen environment after birth, compared with the relatively low-oxygen prenatal environment, is the cause of this change in cardiomyocyte proliferation².

In an exciting new study, Nakada and Canseco et al. built on these previous findings to create conditions that allowed adult mouse hearts to heal after heart attacks³. They found that when adult mice were maintained in an environment of gradually decreasing oxygen, to a prolonged final level of 7% (or roughly equivalent to the air at the top of Mt. Everest), their cardiomyocytes began dividing and actually repaired the damage from an induced heart attack. If this phenomenon also holds true for human hearts and it can be controlled to allow treatment of heart attack patients, the potential health benefits would be enormous.

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Bibliography

1. Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA. (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078-80.
2. Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA, Santos CX, Thet S, Mori E, Kinter MT, Rindler PM, Zacchigna S, Mukherjee S, Chen DJ, Mahmoud AI, Giacca M, Rabinovitch PS, Aroumougame A, Shah AM, Szweda LI, Sadek HA. (2014) The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 157:565-79.
3. Nakada Y, Canseco DC, Thet S, Abdisalaam S, Asaithamby A, Santos CX, Shah A, Zhang H, Faber JE, Kinter MT, Szweda LI, Xing C, Deberardinis R, Oz O, Lu Z, Zhang CC, Kimura W, Sadek HA. (2016) Hypoxia induces heart regeneration in adult mice. Nature (Epub ahead of print)