New Way To Treat Heart Failure By Targeting Cardiac Fibrosis, Study Reveals

As the global population ages, the incidence of heart failure is rapidly rising, largely driven by the excessive growth of fibrotic tissue within the heart, known as fibrosis. A groundbreaking study from the Nagoya University Graduate School of Medicine in Japan has identified a key player in this process—an enzyme called protein kinase N (PKN)—which could unlock new avenues for treating heart failure.

The researchers discovered that PKN regulates the conversion of heart fibroblasts to myofibroblasts, a process that threatens the structural integrity of the heart. The study, led by Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara, demonstrated that deleting this enzyme in mice models significantly reduced cardiac dysfunction, indicating the potential of anti-PKN therapies in protecting heart failure patients.

Fibroblasts are small cells responsible for maintaining the structure of the heart. After an injury, these cells often convert into myofibroblasts, which aid in wound healing by producing fibrous connective tissues such as collagen and elastin. In patients with heart failure, however, this process becomes excessive, leading to the accumulation of tissue, a condition referred to as fibrosis. Fibrosis causes the heart tissue to stiffen, impairing its ability to function properly, thus increasing the risk of heart attack.

The team from Nagoya University focused on the role of PKN in this process. Collaborating with researchers at the Max Planck Institute, they discovered that PKN is involved in the signaling cascade that leads to the activation of heart fibroblasts. There are three forms of PKN in mammal cells—PKN1, PKN2, and PKN3—but the study zeroed in on PKN1 and PKN2 due to their presence in heart fibroblasts.

Through experiments involving mice that were genetically modified to lack PKN1 and PKN2, the team found a marked decrease in the expression of actin and collagen, proteins essential for tissue buildup in fibrosis. Additionally, these mice did not exhibit the conversion of fibroblasts to myofibroblasts, indicating that targeting PKN could prevent fibrosis-related cardiac dysfunction.

While the study was conducted on mouse models, the researchers believe their findings have direct implications for human heart health. Dr. Yoshida commented, "Although our study was done in a mouse model, PKN expression has been demonstrated in human heart fibroblasts, so similar results are expected in human trials. Almost all heart diseases are closely linked to heart fibrosis, so we hope our findings will contribute to improving the prognosis for many heart diseases, especially heart failure."

Currently, there are no treatments specifically targeting PKN, but the research team hopes that their discovery will lead to the development of PKN inhibitors. Such inhibitors could represent a new class of treatment, helping to protect patients from the devastating effects of heart failure by preventing fibrosis.

While exciting breakthroughs in heart failure treatment are on the horizon, maintaining a heart-healthy lifestyle is crucial for reducing your risk of heart disease. Here are some daily practices to help protect your heart:

1. Engage in moderate physical activity, such as brisk walking, for at least 30 minutes a day.

2. Focus on a diet rich in fruits, vegetables, whole grains, and lean proteins. Limiting your intake of salt, sugar, and unhealthy fats is essential for heart health.

3. Chronic stress can contribute to high blood pressure and heart disease. Practice relaxation techniques such as meditation or deep breathing.

4. Smoking is a major risk factor for heart disease. Seek support if you need help quitting.

5. Keep an eye on your blood pressure and cholesterol levels to detect any early signs of heart disease.