Diseased heart muscle cells have abnormally shortened telomeres

People with a form of heart disease called cardiomyopathy have abnormally short telomeres in heart muscle cells responsible for contraction, according to a new study by researchers.

Although it’s not yet known whether the stunted telomeres directly affect the function of the cardiomyocytes or arise as a result of heart failure, the finding opens the door to an intriguing line of research and drug discovery. It also may one day allow researchers and clinicians to identify people at risk for heart failure due to cardiomyopathy.

In most cells, telomeres naturally shorten each time the cell divides. But cardiomyocytes divide infrequently, and their telomere lengths remain relatively stable throughout one’s life.

“Because we found in a previous study that cardiomyocytes from boys who had died of Duchenne muscular dystrophy had telomeres that were about 50 percent shorter than those from individuals without the disease,” the senior author said, “we wondered whether people with other genetic heart conditions, such as cardiomyopathies, might also have cardiomyocytes with abnormally shortened telomeres.”

A cardiomyopathy is a condition in which the heart is unusually large, thickened or stiff. This affects its ability to pump blood effectively. One out of every 500-2,500 people worldwide is affected, and cardiomyopathies are a leading cause for heart transplantation. Dilated cardiomyopathy occurs when the left ventricle is enlarged, while hypertrophic cardiomyopathy is caused by a thickening of the heart muscle.

Researchers compared the telomere length in cardiomyocytes from 11 patients with dilated or hypertrophic cardiomyopathy due to genetic mutations with nine people who had died from causes unrelated to heart disease. They found that telomeres from the cardiomyopathy patients were about 25-40 percent shorter than those of the control subjects. In contrast, the telomere length in nonbeating heart cells of the blood vessels did not vary significantly between the two groups.

They saw similar results in cardiomyocytes generated from induced pluripotent stem cells: Those generated from people with cardiomyopathies had significantly shorter telomeres than those generated from unaffected relatives.

“Within 20 days we could see the telomere shortening happening in the laboratory-grown cardiomyocytes from diseased patients, suggesting this is a cell-intrinsic property,” the senior author said.

The ability to use iPS cell technology to generate affected cardiomyocytes also means that it should be possible to quickly and easily test for compounds or drugs that interfere with the telomere shortening with a view to finding drugs to abrogate the disease in humans, the researchers believe.