As society ages, the number of patients with heart failure is rapidly increasing. Excessive fibrosis of the heart, known as fibrosis, is associated with the progression of heart failure. Recently, a research team from Nagoya University Graduate School of Medicine (Japan) found an enzyme called protein kinase N (PKN), which regulates cardiac fibrosis. This enzyme catalyzes the conversion of cardiac fibroblasts into myofibroblasts, which threatens the integrity of the heart. Deleting this enzyme reduced cardiac dysfunction, suggesting the potential of anti-PKN treatments as a promising therapy to protect patients from heart failure. The findings of the study were published in the journal  Nature Communications.

The heart uses small cells called fibroblasts to maintain its integrity, and after injury, they are usually transformed into myofibroblasts, which aid in wound healing by producing fibrous connective tissues such as collagen and elastin. However, in patients with heart failure, they often cause excessive tissue buildup, leading to tissue stiffness and impaired heart function. This condition, known as cardiac fibrosis, causes the heart’s structural integrity to deteriorate, increasing the risk of heart attack.

The enzyme PKN was found to be involved in the signaling cascade that induces cardiac fibroblast activation.

The research team, led by Drs. Satoya Yoshida, Mikito Takefuji and Toyoaki Murohara of the Department of Cardiology at Nagoya University, suspected the involvement of PKN in the process of fibroblast-to-myofibroblast conversion that causes cardiac fibrosis. They also collaborated with colleagues at the Max Planck Institute to study its role and to clarify the cause.

In mammalian cells, there are three forms of PKN: PKN1, 2, and 3. Using RNA sequencing data, they identified PKN1 and 2 in cardiac fibroblasts. The study used mice that were bred without PKN1 and PKN2. The researchers found that although cardiac function was not affected, there was a significant reduction in actin and collagen expression in myocardial infarction and heart failure models of cardiac fibrosis. These proteins are essential components responsible for tissue accumulation. They also found that mice with PKN1 and 2 inhibition did not show fibroblast transformation into myofibroblasts. “Although our study was performed in a mouse model, PKN expression has been demonstrated in human cardiac fibroblasts, so similar results are expected in clinical trials ,” said Dr. Yoshida. “ In fact, most heart diseases are closely related to cardiac fibrosis. I believe that our findings contribute to improving the prognosis of many heart diseases, especially heart failure .”

Currently, there are no treatments that target PKN. However, the team hopes that their findings will lead to the development of PKN inhibitors. Such inhibitors would be a new treatment for patients at risk of heart failure.

                     Source: NASATI, PTT (NASATI), according to https://medicalxpress.com/ October 2024