An increase in connective tissue, termed cardiac fibrosis, is a hallmark of the stiff heart which is associated with heart failure. Currently, there is no treatment for cardiac fibrosis. Therefore, it is critical to understand the molecular players involved in cardiac fibrosis to develop new therapies.
The connective tissue contains proteins with sugar chains, such as versican. Versican has been suggested to be a target for treatment of the stiff heart. However, how versican regulates cardiac fibrosis is unknown. To understand this in detail, firstly, we need to assess the production of versican during cardiac fibrosis. Thus, we have examined the regulation and localization of versican, as well as the cleaved fragment of versican at different time points after induction of pressure overload in mice, in cell cultures, and in myocardial samples from patients with a particular type of heart failure, termed cardiomyopathy.
We found that versican increases in the early phase of fibrosis development, whereas the cleaved fragment increases in the late phase of fibrosis development. Further, both versican and the cleaved fragment accumulates in the fibrotic regions of the heart during pressure overload and in patients with cardiomyopathy. Taken together, our data indicate that versican and its cleaved fragment are key players involved in the development of cardiac fibrosis. However, we need further studies to examine the mechanistic role of versican and its cleaved fragment in cardiac fibrosis.
The graphical abstract shows the production of versican and its cleaved fragment, DPEAAE, during cardiac fibrosis development. In control mice (left panel), the production of versican and DPEAAE is low in the heart. However, in the cardiac pressure overload model (middle panel), the production of versican (orange color) increases immediately after pressure overload. This increase in versican production is mainly caused by cells that produce collagen, a marker of fibrosis, during fibrosis development. In addition, DPEAAE (blue color) is increased in the late phase of cardiac fibrosis. Further, we found that versican is accumulated around the vessels before the development of perivascular and interstitial fibrosis (increased accumulation of connective tissue between the cells). In patients with cardiomyopathy (right panel), increased amounts of versican and DPEAAE are observed in the fibrotic regions of the myocardium.
Matrix Biology Plus
PubMed 38076279, DOI 10.1016/j.mbplus.2023.100135
