16 september 2024 : As the population ages, heart failure cases are increasing. A key factor in the progression of heart failure is fibrosis, characterized by excessive growth of fibrotic tissue in the heart. Researchers from the Nagoya University Graduate School of Medicine in Japan have identified an enzyme called protein kinase N (PKN) as a crucial regulator of cardiac fibrosis.
PKN promotes the conversion of heart fibroblasts into myofibroblasts, which compromise the heart’s structural integrity. Inhibiting this enzyme led to reduced ventricular dysfunction, suggesting that therapies targeting PKN could be effective in preventing heart failure.
Fibroblasts, small cells in the heart, normally help maintain its structure. They transform into myofibroblasts in response to damage, which then produce fibrous tissues like collagen and elastin to aid healing. However, in heart failure, these cells can proliferate excessively, leading to tissue hardening and impaired function, known as fibrosis, which increases the risk of heart attack.
The enzyme PKN is involved in a signaling pathway that activates heart fibroblasts. Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara, along with colleagues from the Max Planck Institute, investigated PKN’s role in fibrosis. They found that PKN1 and PKN2 are present in heart fibroblasts. Experiments with mice lacking these enzymes showed a significant reduction in actin and collagen levels—key proteins involved in fibrosis—without affecting overall heart function. Mice with suppressed PKN1 and PKN2 also did not exhibit fibroblast-to-myofibroblast conversion.
Dr. Yoshida noted that while the study was conducted in mice, PKN expression has been observed in human heart fibroblasts, suggesting that similar outcomes may occur in human trials. He believes these findings could significantly improve the prognosis for various heart diseases, particularly heart failure.