A Link Between Hypoxia and Muscle Regeneration

Creating a low-oxygen environment could lead to repair not only of heart muscle, but of other organs as well.

New research says that heart muscles can regenerate in a low oxygene environments. These findings, published in the journal Nature, build upon years of work which began with the discovery that the hearts of newborn mammals have the ability to regenerate, similar to the way skin has the ability to repair itself after a cut.

But this ability of heart muscle to regenerate is quickly lost in the following weeks as the animal ages and cardiomyocytes are bathed in the oxygen-rich environment of the beating heart, causing damage to the cells.

“The adult human heart is not capable of any meaningful repair following a heart attack, which is why heart attacks have such a devastating impact,” said Dr. Hesham Sadek, Associate Professor of Internal Medicine.

Normal, healthy heart muscle is well supplied with oxygen-rich blood. However, cardiologists have been able to regenerate heart muscle by placing mice in an extremely low-oxygen environment.

Researchers with the Hamon Center for Regenerative Science and Medicine gradually lowered the oxygen in the air breathed by mice until it was at 7% — about the concentration of oxygen at the top of Mt. Everest.

After two weeks in the low-oxygen environment, the heart muscle cells, called cardiomyocytes, were dividing and growing; which is incredible because, under normal circumstances, cardiomyocytes do not divide in adult mammals.

“Though counterintuitive, we’ve shown that severely lowering oxygen exposure can sidestep damage to cells caused by oxygen and turn cell division back on, leading to heart regrowth,” said Dr. Sadek.

In this study, researchers lowered the oxygen level from the normal 21% to 7% over a period of weeks, then monitored the mass and function of the heart. They demonstrated that reduction in oxygen leads to both an increase in cardiomyocytes and improved heart function.

The researchers had tried a 10% oxygen environment, but there was no heart regrowth in the 10% To avoid oxygen damage to cells, oxygen levels needed to be very lowent oxygen environment; a situation referred to as hypoxia.

“This work shows that hypoxia equivalent to the summit of Mt. Everest can actually reverse heart disease, and that is extraordinary,” said Dr. Benjamin Levine, Professor of Internal Medicine.

According to Dr. Sadek, in theory, creating a low-oxygen environment could lead to repair not only of heart muscle, but of other organs as well. Although exposure to this level of hypoxia can result in complications, it can be tolerated in human when performed in a controlled setting.