Research Article The small leucine-rich proteoglycan fibromodulin exerts anti-fibrotic effects in cultured human cardiac fibroblasts

Cardiac fibrosis is common and detrimental in numerous heart diseases, affecting millions of patients worldwide. Cardiac fibrosis is characterized by excessive production of extracellular matrix (ECM) constituents such as fibrillar collagens, produced by activated cardiac fibroblasts, i.e.: myofibroblasts. Therapeutic targeting of cardiac fibrosis is highly attractive; however, it remains a major medical challenge. Fibromodulin is a small leucine-rich proteoglycan localized in the ECM. Fibromodulin binds to collagen fibrils, and plays a critical role in collagen fibrillogenesis, ECM organization, wound healing and regulation of the pro-fibrotic cytokine transforming growth factor beta (TGF) in several organs. Fibromodulin is highly upregulated in mice and patients with heart failure, but little is known about its role in cardiac fibrosis. Our recent findings from primary cultures of cardiac fibroblasts from neonatal rat hearts suggest that fibromodulin has anti-fibrotic effects.