An enzyme responsible for converting heart fibroblasts into myofibroblasts has been found to compromise the heart’s integrity, according to a new study published in Nature Communications. The research suggests that targeting this enzyme could offer a promising therapeutic approach for protecting patients from heart failure.
The heart’s integrity is maintained by fibroblasts, small cells that are often transformed into myofibroblasts in response to injury. Myofibroblasts promote wound healing by producing fibrous connective tissues, such as collagen and elastin. However, in heart failure patients, these cells often accumulate excessively, leading to tissue hardening, a condition known as fibrosis. This process compromises the heart’s structure and increases the risk of heart attack.
The enzyme PKN has been implicated in a signaling cascade that activates heart fibroblasts. A research team led by Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara from the Department of Cardiology at the Nagoya University Graduate School of Medicine suspected PKN’s role in the conversion of fibroblasts to myofibroblasts in fibrosis. Collaborating with colleagues at the Max Planck Institute, they explored its involvement.
In mammalian cells, there are three forms of PKN: PKN1, PKN2, and PKN3. Using RNA sequencing data, the researchers identified PKN1 and PKN2 in heart fibroblasts. They then studied mice lacking PKN1 and PKN2. The results showed that, although heart function remained unaffected, there was a significant reduction in the expression of actin and collagen—key proteins responsible for the tissue buildup seen in fibrosis. The researchers also found that fibroblasts in these mice did not convert into myofibroblasts.
“Although our study was conducted in a mouse model, PKN expression has been shown in human heart fibroblasts, so similar results can be expected in human trials,” said Dr. Yoshida. “In fact, almost all heart diseases are closely associated with heart fibrosis, and I believe our findings will contribute to improving the prognosis of many heart conditions, particularly heart failure.”
(ANI)