Scientists have found a new clue that could lead to better treatments for heart failure, especially in people with type 2 diabetes.
A recent study published in Cellular and Molecular Life Sciences highlights the protective role of a protein called GADD45A in the heart. Researchers say boosting this protein’s activity might help stop the harmful changes that lead to heart failure.
Heart failure often begins with a condition called cardiac hypertrophy, where the heart’s muscle wall thickens in response to extra strain.
This is the heart’s way of coping with increased pressure—like high blood pressure or obesity—but when the stress continues over time, this adaptive response turns harmful.
The heart may become enlarged, its function can weaken, and eventually, it may lead to serious heart failure.
People with diabetes are especially at risk because they commonly have other conditions that put pressure on the heart, including high blood pressure and coronary artery disease. In this new study, researchers from the University of Barcelona and affiliated institutions studied the role of the GADD45A protein in heart health.
GADD45A is known for responding to stress and damage in cells. While it has previously been linked to cancer prevention and metabolism, this is the first time it has been strongly connected to heart function.
Using both mouse models and human heart cells, the team discovered that when GADD45A was missing, the mice developed more inflammation, more fibrosis (a type of scarring in the heart), and greater cell death in the heart muscle. These changes were linked to overactivation of three key molecules known to drive harmful inflammation and scarring: AP-1, NF-κB, and STAT3.
The absence of GADD45A also led to pronounced thickening of the heart muscle and a decline in heart function. In contrast, when scientists increased the amount of GADD45A in human heart cells, they saw a partial reversal of the harmful effects triggered by a pro-inflammatory molecule called TNF-alpha.
The findings suggest that GADD45A helps protect the heart by reducing inflammation, preventing scarring, and supporting healthy heart muscle cells. This could be a major breakthrough, as inflammation and fibrosis are known to play key roles in the worsening of heart failure.
This research builds on earlier work showing that GADD45A can also help regulate metabolism and prevent harmful changes in other tissues. Some studies even suggest it might help prevent obesity and type 2 diabetes.
While more research is needed, scientists believe this discovery could open the door to a new kind of heart failure treatment—one that protects the heart from the inside by boosting its natural defense systems.
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