NAGOYA: As society ages, the number of patients suffering from heart failure grows significantly. Fibrosis, or excessive growth of fibrotic tissue in the heart, has been linked to the advancement of heart failure. A group from Nagoya University Graduate School of Medicine in Japan discovered an enzyme called protein kinase N (PKN) that controls cardiac fibrosis.
The enzyme converts heart fibroblasts to myofibroblasts, putting the heart’s integrity at risk. Deleting this enzyme reduced ventricular dysfunction, indicating that anti-PKN therapies are a prospective therapy for protecting patients from heart failure.
The findings were published in Nature Communications.
The heart maintains its integrity by the usage of tiny cells known as fibroblasts, which are frequently transformed into myofibroblasts following damage. Myofibroblasts promote wound healing by creating fibrous connective tissues like collagen and elastin. However, in heart failure patients, they frequently cause extra tissue to collect, resulting in hardening of heart tissue and reduced function, a disease known as fibrosis. This process reduces the integrity of the heart’s structure, increasing the risk of a heart attack.
The enzyme PKN has been implicated in a signaling cascade that causes heart fibroblast activation. A group led by Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara in the Department of Cardiology at the Nagoya University Graduate School of Medicine suspected the involvement of PKN in the changes of fibroblasts to myofibroblasts seen in fibrosis. In collaboration with colleagues at the Max Planck Institute, they investigated its role.
In mammal cells, there are three forms of PKN: PKN1, 2, and 3. Using RNA-sequencing data, they identified PKN1 and 2 in heart fibroblasts. The study used mice raised without PKN1 and PKN2. 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 PKN1 and 2 did not show conversion of fibroblasts to myofibroblasts.
“Although our study was done in a mouse model, PKN expression has been demonstrated in human heart fibroblasts, so similar results are expected in human trials,” Dr. Yoshida said. “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.”
The enzyme converts heart fibroblasts to myofibroblasts, putting the heart’s integrity at risk. Deleting this enzyme reduced ventricular dysfunction, indicating that anti-PKN therapies are a prospective therapy for protecting patients from heart failure.
The findings were published in Nature Communications.
The heart maintains its integrity by the usage of tiny cells known as fibroblasts, which are frequently transformed into myofibroblasts following damage. Myofibroblasts promote wound healing by creating fibrous connective tissues like collagen and elastin. However, in heart failure patients, they frequently cause extra tissue to collect, resulting in hardening of heart tissue and reduced function, a disease known as fibrosis. This process reduces the integrity of the heart’s structure, increasing the risk of a heart attack.
The enzyme PKN has been implicated in a signaling cascade that causes heart fibroblast activation. A group led by Drs. Satoya Yoshida, Mikito Takefuji, and Toyoaki Murohara in the Department of Cardiology at the Nagoya University Graduate School of Medicine suspected the involvement of PKN in the changes of fibroblasts to myofibroblasts seen in fibrosis. In collaboration with colleagues at the Max Planck Institute, they investigated its role.
In mammal cells, there are three forms of PKN: PKN1, 2, and 3. Using RNA-sequencing data, they identified PKN1 and 2 in heart fibroblasts. The study used mice raised without PKN1 and PKN2. 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 PKN1 and 2 did not show conversion of fibroblasts to myofibroblasts.
“Although our study was done in a mouse model, PKN expression has been demonstrated in human heart fibroblasts, so similar results are expected in human trials,” Dr. Yoshida said. “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.”
