Scientists reverse heart failure via newly discovered regeneration pathway

Print 10 October 2017
Carly Helfand / Fierce Pharma

A signaling pathway in the body called Hippo is well known in scientific circles for its potential role in cancer, but now scientists at Baylor believe they have found another place where manipulating this system could be beneficial—the heart.

Hippo signaling can prevent damaged heart muscle from repairing itself. So the Baylor researchers wanted to see what would happen if they turned off the pathway altogether. When they silenced Hippo for 6 weeks in mouse models of heart failure, they were able to restore pumping ability to that of healthy hearts, according to a press release. The research was published in the journal Nature.

Because blood flow stops during a heart attack, muscle tissue can die. That dead muscle is replaced by scar tissue that’s unable to help the heart to pump. Over time, the heart continues to weaken, leading to chronic heart failure in most people. The Baylor team recognized that Hippo signaling activity increases during a heart attack, suggesting a link between the pathway and the heart’s inability to repair itself.

The effort to find new ways of combating heart disease is largely aimed at promoting regeneration of damaged heart muscle. In May, Japanese scientists identified a signaling protein called urocortin2 (Ucn2) that’s elevated in people with chronic heart failure. When they used this protein to silence another protein called corticotropin-releasing hormone receptor 2 (Crhr2), they were able to prevent the loss of cardiac function in mouse models.

Cell therapy is also a potential treatment for heart failure. In the spring, Australian biotech company Mesoblast released positive data from a trial of mesenchymal precursor cells (MPCs) that are delivered straight into the left ventricular muscle of heart failure patients. Several other companies are investigating different cell-based approaches to promoting heart regeneration.

The scientists at Baylor have a theory about why inhibiting the Hippo pathway might prove to be an effective regenerative therapy: It seems to alter the abnormal thickening of the heart muscle, or “fibrosis,” that is seen in heart failure, in addition to encouraging cardiac muscle cells to grow and survive in injured hearts. The team plans further studies to shed light on how inhibiting Hippo affects fibrosis.

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