Reversal of heart scarring may be possible
By Ruth SoRelle, M.P.H.
A condition called cardiac fibrosis (which refers to scarring of the heart) can slow the organ, eventually preventing it from pumping blood.
Previously, experts thought that the end result was inevitable, but new research indicates that the process may be reversible, said a Baylor College of Medicine scientist in a commentary in a recent issue of the New England Journal of Medicine.
Based on recent study in the journal Nature Medicine by Harvard Medical School researchers and other work in the field, Jeffrey Towbin, M.D., Ph.D., professor of pediatrics - cardiology at BCM and chief of pediatric cardiology and director of the Pediatric Cardiomyopathy and Heart Failure Service at Texas Children's Hospital, wrote that "like many 'sure things' in medicine and science, we must reconsider whether the development of cardiac fibrosis and the untoward effects it has on cardiac function, is indeed an irreversible event."
Dead heart not always dead
"In cardiology, when talking about the heart as a pump, we always considered that a dead heart is dead (forever). That's clearly untrue. This Nature Medicine article describes a basic science example of how that reversibility occurs."
Recent work at unraveling the mechanisms behind such scarring points the way to novel treatments that may block the source of the scars that hinder the heart's work, he writes.
"The TGF (transforming growth factor) beta pathway in the cell is not only the scar-forming pathway but it can be reversed when interrupted by BMP (bone morphogenic protein)," he said.
"Think about it in a backwards approach," he said. "Consider a heart with dilated cardiomyopathy (an extremely enlarged and weakened heart) with a scar. Why can't you "play" with the cellular pathways to get rid of the scarring as well as increasing the thickness of ventricle (the heart's pumping chamber), which has been thinned by an infarct (or heart attack) or other abnormality?"
Causes of heart scarring
Many heart problems can cause heart scarring, including narrowing of the arteries, resulting in reduced blood flow to the heart itself; heart attack; diseases that weaken the heart muscle, and inflammation of that same muscle. While there are drugs that treat the symptoms, too often the heart suffers a devastating rhythm abnormality or loses pumping ability. The patient dies because of the inability of the heart to pump effectively, Towbin writes.
However, research shows that the scarring disrupts the very cells from which heart muscle is built, where excessive amounts of proteins accumulate and interfere with their proper function. Fibroblasts – the source of connective tissue and scaffold or matrix of many tissues – play a critical role in this scarring. A recent study shows that in heart scarring, fibroblasts from bone-marrow and epithelial (skin and other materials that line the outer and inner surfaces of the body) cells contribute to this disabling accumulation. Previously, it was thought that the fibroblasts in the heart were derived from a form of embryonic cell and that they were the source of any increase in cell population.
New fibroblasts
The process by which these new fibroblasts arise is called endothelial-mesenchymal transition, a process that plays a key role in the development of the embryonic heart. The Harvard researchers proved that this process plays a role in increasing the pool of heart fibroblasts. In their mice, a protein called transforming growth factor-beta 1, induced the formation of these fibroblasts from epithelial and bone marrow origins. Another protein – bone morphogenic protein-7 – prevented the cells' transition to fibroblasts.
"The TGF-beta superfamily has more than 40 members, including TGF-beta, growth differentiation factors and BMPs," Towbin writes. "Members of this superfamily seem to drive fibrosis in heart, kidneys, lungs and liver."
He concludes: "Novel treatment, perhaps combined with the use of old stand-bys such as ACE inhibitors, which intervene in the TGF-beta pathway, could help in the battle to preserve cardiac function in those with ischemic heart disease, acquired forms of the diseases such as myocarditis as well as genetic-based cardiomyopathies."
The Nature Medicine paper can be found at http://www.nature.com/nm/journal/v13/n8/abs/nm1613.html;
jsessionid=D80CB2B62AB671EB325E7083351B9211.
Towbin's commentary is at http://content.nejm.org/cgi/reprint/357/17/1767.pdf
