As the population ages, there’s a significant rise in the number of individuals suffering from heart failure. This condition progresses due to an overgrowth of fibrotic tissue within the heart, referred to as fibrosis. Researchers at the Nagoya University Graduate School of Medicine in Japan have discovered that an enzyme known as protein kinase N (PKN) plays a key role in regulating heart fibrosis. With no existing treatments that specifically target PKN, managing this enzyme presents a promising opportunity for new therapies aimed at combatting heart failure.
With a growing elderly population, there is a sharp rise in heart failure cases. The condition is linked with the excessive formation of fibrotic tissue in the heart, termed fibrosis. Researchers from Nagoya University in Japan have identified the enzyme protein kinase N (PKN) as a regulator of this fibrosis. PKN facilitates the transformation of heart fibroblasts into myofibroblasts, which can compromise the heart’s structure. Eliminating this enzyme has been shown to lessen cardiac dysfunction, suggesting that anti-PKN treatments could serve as an effective strategy to protect those at risk of heart failure. The findings were shared in an article in Nature Communications.
The heart employs specialized cells called fibroblasts to uphold its structure, and these cells often convert into myofibroblasts following injury. Myofibroblasts play a vital role in healing by generating fibrous tissues like collagen and elastin. However, in individuals with heart failure, they can produce an overabundance of tissue, leading to the stiffening of the heart—a condition identified as fibrosis. This ongoing process weakens the heart’s structural integrity and raises the chances of a heart attack.
The enzyme PKN is part of a signaling pathway implicated in the activation of heart fibroblasts. A research team led by Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara at Nagoya University posited that PKN might be involved in the transformation of fibroblasts into myofibroblasts seen in fibrosis. Together with their colleagues from the Max Planck Institute, they explored its function.
In mammalian cells, there are three types of PKN: PKN1, PKN2, and PKN3. Through RNA sequencing, the team identified PKN1 and PKN2 in heart fibroblasts. They conducted their study on mice lacking both PKN1 and PKN2 and found that heart function remained stable, but there was a significant reduction in the levels of actin and collagen—key proteins linked to the tissue buildup associated with fibrosis. The research also revealed that mice with diminished PKN1 and PKN2 did not experience the transformation of fibroblasts into myofibroblasts.
“Even though our study was conducted on mice, PKN has been observed in human heart fibroblasts, leading us to anticipate similar outcomes in human clinical trials,” remarked Dr. Yoshida. “Almost every type of heart disease is closely tied with heart fibrosis, and I believe our research could enhance the outlook for many heart-related conditions, particularly heart failure.”
Currently, there are no treatments specifically targeting PKN. However, the research team aspires that their discoveries will pave the way for the creation of PKN inhibitors, marking a new frontier in treatment for individuals susceptible to heart failure.
