The heart, an extraordinary muscle, beats tirelessly at 60 to 100 times a minute, day and night. But when it weakens, the repercussions can be grave—causing everything from crippling shortness of breath and leg swelling to fluid in the lungs and even death.

Systolic Heart Failure: The Heart’s Struggle to Pump

In systolic heart failure, which affects more than 32 million people globally, the muscle loses the ability to squeeze hard enough to push oxygenated blood from the heart’s left ventricle through the body via the circulatory system.

“The current treatments cardiologists use manage the symptoms of systolic heart failure and are crucial for improving patients’ quality of life,” said Junco Warren, a cardiovascular scientist in the Center for Vascular and Heart Research at the Fralin Biomedical Research Institute at VTC. “However, these therapies don’t directly address the underlying problem — the weakened heart muscle itself. High mortality and hospitalization rates of patients with systolic dysfunction persist. My goal is to find ways to restore heart muscle function, including improving its energy metabolism.”

Warren has identified a protein with the potential to do just that.

PERM1: A Promising Protein in the Fight Against Systolic Heart Failure

In a study published this month the American Journal of Physiology, Warren and her lab show for the first time that a protein known as PERM1 effectively regulates both energy and the heart’s ability to contract. The study suggests the protein could be a new therapeutic approach to systolic heart failure (1^✔ ✔Trusted Source
Adeno-associated virus-mediated gene delivery of Perm1 enhances cardiac contractility in mice

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In recent decades, scientists have developed several drugs aimed at improving heart muscle contraction. But many of the drugs have faced challenges in significantly improving long-term health, and most failed to improve survival in clinical trials, according to a review in the European Journal of Heart Failure.

These drugs intended to either increase the force of the heart’s contractions or improve the efficiency of muscle fiber contractions, said Warren, who is also an assistant professor in Virginia Tech’s Department of Human Nutrition, Foods, and Exercise in the College of Agriculture and Life Sciences. However, both approaches increase energy utilization and can actually worsen patient outcomes.

Systolic heart failure results from a vicious cycle, she said. The heart muscle grows weak, and that in turn inhibits the mitochondria – the energy producers in cells – from doing their job, which further weakens the muscle.

PERM1 Offers New Hope for Systolic Heart Failure Treatment

According to Warren’s findings, a protein called PERM1 regulates both parts of that vicious cycle. PERM1 is found in the heart and skeletal muscles and is known to regulate mitochondrial function. Because the protein is found in muscles that contract, Warren and her team found that the protein might also affect muscle contraction.

“The heart is a unique organ. It beats 24 hours, seven days a week, no rest,” Warren said. “So, the heart’s metabolism must be different from other organs.”

In the study, the researchers delivered the protein into the hearts of healthy mice using a disarmed virus, called adenovirus. Viruses are effective vehicles because they are designed to find their way into difficult places in the body.

New Treatment for Failing Hearts

The study found that the protein regulated the mitochondrial function, as was known, but also improved the heart’s ability to contract.

The research was conducted in healthy hearts, so the next step is to see if the protein has the same impacts in a failing heart.

“Now we are applying this method in failing hearts to see if delivering PERM1 via adeno-associated virus — a method commonly used for gene therapy — is able to bring back cardiac function and mitochondrial function,” Warren said. “That would further suggest that it may be a new therapeutic to treat systolic heart failure by simultaneously addressing the weakness in the muscle and energy production by the mitochondria.”

References:

1. Adeno-associated virus-mediated gene delivery of Perm1 enhances cardiac contractility in mice – (https://journals.physiology.org/doi/abs/10.1152/ajpheart.00545.2024)

Source-Eurekalert