Scientists discover that, in mice, heart scarring is caused by endothelial-mesenchymal transition, and rhBMP7 can repair the damage.
Researchers at Beth Israel Deaconess Medical Center (BIDMC) further elucidated the origins of cardiac fibrosis, a scarring of the heart tissue that leads to a variety of cardiac diseases, most notably heart failure. The study also demonstrated that a molecule known as recombinant human bone morphogenic protein 7 (rhBMP7) can reverse the cardiac fibrosis process.
Fibrosis develops when the body’s natural wound-healing process goes awry. Under normal conditions, specialized cells known as fibroblasts deposit layers of collagen protein to form a scar and thereby enable wounds to heal. However, in abnormal circumstances and for unknown reasons, excessive production of matrix proteins such as collagen, results in pathological scarring or fibrosis.
The researchers speculated that a specialized form of epithelial-mesenchymal transition known as endothelial-mesenchymal transition (EndMT) might be the mechanism behind this, so using knockout mice in which endothelial cells had been marked genetically, the investigators confirmed that, during cardiac fibrosis, these cells were indeed converting into activated fibroblasts that were depositing scar material and impeding the proper function and electrical conduction of the heart.
In the second part of the study, the investigators turned to the rhBMP7 protein to determine if it could successfully reverse the EndMT process in mice, reducing the development of fibroblasts and improving heart function.
“The rhBMP-7 protein was quite impressive in its ability to recover the function of damaged hearts,” says Raghu Kalluri, Ph.D., senior author and chief of the division of matrix biology at BIDMC. “These findings provide compelling proof that the process of fibrosis can be reversed in the heart and offers the possibility of new therapies for patients who have developed cardiac fibrosis as the result of myocardial infarction, hypertension, valvular diseases, or heart transplantation.”
The study appears in the July 29 advance online publication of Nature Medicine.