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Researchers discover how to prevent calcification of heart tissue

Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have discovered that calcification of heart muscle tissue is caused when a type of cell called cardiac fibroblasts go awry. The scientists also found that blocking a molecular pathway in cardiac fibroblasts prevents heart calcification in mice.

In bones, cells called osteoblasts create a strong, dense matrix out of calcium and phosphate. Calcification of soft tissues — known as ectopic calcification — is abnormal and occurs with common diseases such as diabetes and chronic kidney disease, as well as with normal aging. But soft tissues don’t have osteoblasts, and scientists have for years sought to understand which type of cells contribute to ectopic calcification.

Credit: Patrick J. Lynch, Wikimedia Commons

Credit: Patrick J. Lynch, Wikimedia Commons

The researchers suspected that cardiac fibroblasts, the most plentiful type of cell in the heart, might play a role in calcification. So they genetically labeled cardiac fibroblasts with a fluorescent red dye and followed the cells in mice after a heart injury. When calcification began one to four weeks later, the fibroblasts had clustered at the spots where calcification was occurring. Instead of acting like normal cardiac fibroblasts, the cells adopted characteristics of cardiac tissue stem cells that then created bone-forming osteoblasts. The researchers then transplanted some of these fibroblasts into healthy mice and observed calcium deposits formed around the clumps of cells.

To understand which molecules might be responsible for shifting the fibroblasts’ identity, the scientists compared the genes of mice that were prone to ectopic calcification with those that didn’t get it. They discovered that the levels of a protein called ENPP1 were especially high in fibroblasts during calcification. And when they blocked ENPP1 with a drug, they were able to prevent heart calcification.

The study identifies for the first time both a cell type and a molecular pathway linked to heart calcification. If the findings hold true in humans, they could lead to a pharmaceutical treatment for ectopic calcification. “Everyone recognizes that calcification of the heart and blood vessels and kidneys is abnormal, but we haven’t had a single drug that can slow down or reverse calcification; our study points to some therapeutic targets,” said Dr. Arjun Deb, the study’s lead author, a UCLA associate professor of cardiology and of molecular, cell and developmental biology.

The researchers are currently collaborating with other UCLA scientists to study whether other types of ectopic calcification can be treated in this manner. Their findings also may help advance understanding of other types of ectopic calcification, including in the kidneys and blood vessels.

Source: UCLA