Animal research documenting that recombinant human bone morphogenetic protein 7 can reverse cardiac fibrosis may lead to strategies to prevent or treat fibrosis and fibrosis-related heart failure, according to an article published online July 29 by Nature Medicine.

“Heart disease is the number-one cause of death in the Western world,” said lead author Elisabeth Zeisberg, MD, a scientist in the Division of Matrix Biology at Beth Israel Deaconess Medical Center, Boston, and an Instructor of Medicine at Harvard Medical School. “And most people who suffer from heart disease have developed scarring of the heart tissue, known as fibrosis.”

Under normal conditions, fibroblasts deposit layers of collagen to form a scar and enable wounds to heal. However, in abnormal circumstances excessive production of matrix proteins such as collagen results in pathological fibrosis. In the heart, accumulation of matrix leaves myocardium stiff and inflexible.

Zeisberg said “While it’s known that fibroblast cells are responsible for cardiac fibrosis, the source of these fibroblasts has remained unknown until now.”

Zeisberg and senior author Raghu Kalluri, PhD, Chief of the Division of Matrix Biology, speculated that endothelial-mesenchymal transition might be the mechanism behind fibrosis.

“Our laboratory has had a longstanding interest in the area of organ fibrosis and the origin of fibroblasts in this setting,” explained Kalluri. “We have previously demonstrated that in the kidney, liver and the lung, epithelial cells under stress can convert into fibroblasts via epithelial-mesenchymal transition.”

So, using knockout mice in which endothelial cells had been marked genetically, the investigators confirmed that during cardiac fibrosis, these cells were converting into activated fibroblasts, which then deposited scar material and impeded proper ventricular function and electrical conduction.

In the second part of the study, the investigators turned to the recombinant protein to determine if it could successfully reverse the process and reduce development of fibroblasts and lead to the improvement of heart function.

“The rhBMP-7 protein was quite impressive in its ability to recover the function of damaged hearts,” said Kalluri. “These findings provide compelling proof that the process of fibrosis can be reversed in the heart and offer the possibility of new therapies for patients who have developed cardiac fibrosis as the result of myocardial infarction, hypertension, valvular diseases or heart transplantation.”