An international team of scientists has found a natural defense system in the body that protects the heart from a serious condition known as heart failure with preserved ejection fraction, or HFpEF.
This type of heart failure is common, especially in older adults, and currently lacks effective treatments.
The discovery could pave the way for new therapies that prevent or even reverse the disease.
The research was led by scientists from the University of Manchester, Baylor College of Medicine, and other institutions.
It was published in the journal Circulation. HFpEF is a complex disease often linked to conditions like obesity, diabetes, and high blood pressure.
One of the major causes is a buildup of harmful fats inside heart cells, known as lipid toxicity, which damages the heart over time.
Dr. Tamer Mohamed, a heart specialist at Baylor, explained that his team used thin slices of human heart tissue affected by HFpEF to understand how fat builds up in the heart. They also studied mice and rats to confirm their findings.
What they discovered was that two specific genes—XBP1 and EDEM2—play a key role in keeping fat levels in heart cells under control.
In patients with HFpEF and in animals exposed to metabolic stress, these two genes were found to be much less active than normal. The researchers then tested what would happen if they turned off these genes in mice. The result: the mice became more sensitive to fat buildup and their heart function worsened, mimicking HFpEF.
But there was good news, too. When the researchers reactivated the genes, the animals’ hearts began to recover. The fat buildup decreased, and their heart function improved. This shows that the XBP1 and EDEM2 genes work together to protect the heart from damage caused by excess fat.
Dr. Mohamed said this natural heart-protecting system could be the key to developing new treatments. By boosting this pathway, doctors might be able to stop HFpEF from progressing—or even reverse it. Since HFpEF is becoming more common and current treatments are limited, this discovery offers hope to millions of people at risk of or already living with the condition.
The team now hopes to explore this pathway further, with the goal of turning their findings into real-world treatments in the near future.
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Source: Baylor College of Medicine.
