Cardiomyopathy, a disease that affects the heart muscle and the way it pumps, affects 50,000 Americans. In cardiomyopathy, the heart muscle becomes enlarged, thick or rigid. In rare cases, the muscle tissue in the heart is replaced with scar tissue.

Different types of cardiomyopathies have different causes. For example, inflammation of the heart muscle can cause inflammatory cardiomyopathy. A heart rhythm problem can cause tachycardia-induced cardiomyopathy. Cardiomyopathy may also occur as a result of damage to the heart, such as from a heart attack.

The adult heart muscle is made of cells called cardiomyocytes, which don't replenish themselves after a heart attack or other significant heart muscle damage.

It was initially believed that cardiomyocytes were unable to replicate themselves and that their total number was firmly set at birth. However, UT Southwestern researchers were able to devise a new cell-tracing technique, allowing them to detect cells that do replenish themselves after being damaged.

This cell does not appear to be a stem cell but rather a specialized cardiomyocyte, or heart muscle cell that can divide. Their previous research revealed that it is the highly oxygenated environment of the heart that prevents most heart muscle cells from dividing.

The researchers reasoned that the cells that do divide must, therefore, be low on oxygen, which is a condition called hypoxic. They then devised a technique to identify and trace the lineage of hypoxic cells. That technique led them to the identification of the proliferating cells within the heart muscle.

The researchers found hypoxic microenvironments with proliferating cells scattered throughout the heart muscle. They found the rate of formation of new cells to be between 0.3 and 1 percent annually.

Traditional fate mapping, which is like developing a family tree for cells, labels cells based on the expression of a certain gene. That didn’t work for the hypoxic cells, which are mainly regulated at the protein level rather than the gene-expression level.

Instead, the researchers developed a sophisticated protein-tracking technique based on the presence of a hypoxia-responsive protein called Hif-1alpha. Researchers developed a genetically modified mouse in which the Hif-1alpha protein is fused to another protein, called Cre recombinase, could then be used for cellular labeling.

According to Dr. Hesham Sadek, assistant professor of internal medicine with the Hamon Center for Regenerative Science and Medicine and senior author of the study, the fate-mapping approach, based on protein stabilization rather than gene expression, is an important tool for studying hypoxia in the whole organism. It can identify any hypoxic cell, not just a cardiomyocyte, so this has broad implications for cellular turnover in any organ.

For decades, researchers have been trying to find the specialized cells that make new muscle cells in the adult heart. Researchers at UT Southwestern firmly believe that they have found that cell. The new technique, or fate mapping, is an equally important development that may prove useful for distinguishing similar regenerating cells in other organs, as well as in cancers.