Datensatz

Zusammenfassung

Chronic fibrotic tissue disrupts various organ functions. Despite
significant advances in therapies, mortality and morbidity due to heart
failure remain high, resulting in poor quality of life. Beyond the
cardiomyocyte-centric view of heart failure, it is now accepted that
alterations in the interstitial extracellular matrix (ECM) also play a
major role in the development of heart failure. Here, we show that
protein kinase N (PKN) is expressed in cardiac fibroblasts. Furthermore,
PKN mediates the conversion of fibroblasts into myofibroblasts, which
plays a central role in secreting large amounts of ECM proteins via p38
phosphorylation signaling. Fibroblast-specific deletion of PKN led to a
reduction of myocardial fibrotic changes and cardiac dysfunction in mice
models of ischemia-reperfusion or heart failure with preserved ejection
fraction. Our results indicate that PKN is a therapeutic target for
cardiac fibrosis in heart failure.