Protein Kinase – A New Target For Treating Heart Failure? Research Finds

As society ages, the number of patients with heart failure is rapidly increasing. A group from the Nagoya University Graduate School of Medicine in Japan has found an enzyme protein kinase N (PKN) that regulates heart fibrosis. The enzyme catalyzes the conversion of heart fibroblasts to myofibroblasts, which threatens the integrity of the heart. Deleting this enzyme reduced cardiac dysfunction, indicating the potential of anti-PKN treatments as a promising therapeutic for protecting patients against heart failure. The study was published in Nature Communications.

The enzyme protein kinase N (PKN) has been implicated in a signaling cascade that causes heart fibroblast activation. A group of researchers in the Department of Cardiology at the Nagoya University Graduate School of Medicine suspected the involvement of protein kinase N (PKN) in the changes of fibroblasts to myofibroblasts seen in fibrosis. 

In mammal cells, there are three forms of protein kinase N (PKN): protein kinase N 1, 2, and 3. Using RNA-sequencing data, they identified protein kinase N 1 and 2 in heart fibroblasts. The study used mice raised without protein kinase N 1 and 2. It found that although heart function remained unaffected, there was a notable decrease in actin and collagen expression in the myocardial infarction and heart failure model. These proteins are essential components responsible for the tissue buildup observed in fibrosis. They also found that mice with suppressed protein kinase N 1 and 2 did not show conversion of fibroblasts to myofibroblasts.

“Although our study was done in a mouse model, protein kinase N (PKN) expression has been demonstrated in human heart fibroblasts, so similar results are expected in human trials,” said Dr. Satoya Yoshida, who co-led the study. “In fact, almost all heart diseases are closely related to heart fibrosis. I believe our findings contribute to improving the prognosis of many heart diseases, especially heart failure.”

Reference: Yoshida, S., Yoshida, T., Inukai, K. et al. Protein kinase N promotes cardiac fibrosis in heart failure by fibroblast-to-myofibroblast conversion. Nat Commun 15, 7638 (2024). https://doi.org/10.1038/s41467-024-52068-0