New knowledge about the heart's healing capacity

A group of researchers from Baylor College of Medicine, the Texas Heart Institute and the University of Texas Health Sciences Center in Houston today reveals in the newspaper Genes and development new knowledge about the newly discovered heart's healing capacity involving the hippopotamus cell pathway. The group previously reported that inactivation of the Hippo pathway in the adult murine heart favored regeneration of the heart muscle after injury, thus opening the possibility of developing promising treatments for heart failure.

In this study, researchers found that inactivation of the hippopotamus pathway in cardiac fibroblasts, non-muscular heart cells intertwined with cardiac muscle cells, favored cardiac fibrosis and negatively affected function heart. These results highlight the need to target the hippopotamus pathway specifically in cardiac muscle cells and not in cardiac fibroblasts for safe and effective treatment against heart failure.

"Heart failure remains the leading cause of death in the United States and one of my lab's interests is to develop ways to heal the heart muscle by studying the cellular pathways involved in development and regeneration. of the heart, "said Dr. James Martin, Corresponding Author, and the Vivian L. Smith Chair in Regenerative Medicine at Baylor and Director of the Cardiomyocyte Renewal Lab at the Texas Heart Institute.

During a heart attack, the blood stops flowing in the heart; without oxygen, part of the heart muscle dies. The heart muscle does not regenerate; instead, it replaces dead tissue with a scar, made up of cells called fibroblasts. If there are too many scars, the heart gradually weakens; a large proportion of people who have had a serious heart attack will develop heat failure and heart scarring.

In previous studies, Martin and his colleagues had discovered that inactivation of the Hippo signaling pathway in adult mouse hearts caused the regeneration of heart muscle cells after a heart attack. These results gave rise to the hope of developing promising therapies for heart failure involving the hippopotamus pathway.

In the present study, Martin and his colleagues further investigated the hippopotamus pathway in the adult mouse heart, focusing this time on its role in heart fibroblasts, non-muscle cells closely associated with cardiac muscle cells. . Researchers conducted a number of baseline studies, including single cell sequencing experiments that resulted in high resolution of their assays.

"We inactivated the hippopotamus pathway in resting adult hearts that showed no lesions and observed that fibroblasts were activated, they multiplied and transformed into myofibroblasts, a major cell type that appears in cardiac tissues. after an injury, "Martin said.

"Mouse hearts with hippopotamus deficient in heart fibroblasts spontaneously developed cardiac fibrosis, even without injury, resulting in severe cardiac dysfunction," said co-lead author, Dr. Yang Xiao, postdoctoral fellow. in the Martin lab during this project. . "This and other evidence indicates that the Hippo pathway is necessary to limit cardiac fibrosis; Hippo is important for keeping fibroblasts at rest."

In addition, the researchers found that inactivation of the hippopotamus pathway also triggered a molecular cascade resulting in an inflammatory response induced by Yap, a molecule regulating multiple molecular pathways.

"We know that Hippo and Yap work together, and Hippo acts as a brake on Yap, so when we took Hippo, Yap stayed active and regulated the expression of important signaling molecules that" speak ". to macrophages and other immune cells, drawing them into the heart process, "Martin said.

The researchers believe they have identified important information about heart function. Their discoveries provide information on genetic pathways important for maintaining resting fibroblasts.