The heart's connective tissue cells turn into bone producers as a reaction to injury, researchers from University of California, Los Angeles' Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have found.

In a study published in the journal Cell Stem Cell, the researchers detailed their discovery, which they said helps shed light on why some of the people who live through heart damage start developing abnormal deposits of calcium, the bone's main component, in the walls or valves of their hearts.

"Heart calcification has been understudied and underreported," said Arjun Deb, senior author for the study.

According to Deb and colleagues, they began their research by looking into heart cells responsible for calcification. And because calcification, fibrosis and tissue injury are all strongly associated with each other, they hypothesized that it's possible cardiac fibroblasts are contributors to the process of calcification.

Cardiac fibroblasts are cells that promote scar tissue after an injury is sustained by the heart.

Heart Calcification Research

For the study, the researchers genetically tagged mice cardiac fibroblasts and observed as the cells started transforming into bone producers after heart injury. Cardiac fibroblasts removed from the calcification region were then transplanted under the skin of healthy mice as soft-tissue calcification occurred. In the lab, human cardiac fibroblasts were seen to have the same calcium deposit-forming capabilities.

Addressing Heart Calcification

The researchers' best lead against heart calcification is a drug target called ENPP1, a protein the heart overexpresses and is particularly produced in large quantities by cardiac fibroblasts in the event of an injury. When the researchers tried to disrupt ENPP1 activity by injecting several different small molecules into the sample, they found that calcium deposits were reduced by at least 50 percent. When a drug known as etidronate was injected, the researchers observed a 100 percent rescue without calcification after a heart injury.

Future Heart Calcification Studies

According to Deb, the researchers are now looking into whether or not their discovery is a common pathway for calcification and if targeting ENPP1 could be be applied to tissues from other parts of the body. They are also exploring how to prevent calcification in blood vessels and reversing calcification, as the small molecule approach was only able to keep deposits of calcium at bay when used prior to heart injury.

The current study received funding support from a James Eason Cardiovascular Discovery Award, the U.S. Department of Defense, the Oppenheimer Foundation, the California Institute for Regenerative Medicine and the National Institutes of Health.

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