Decorin, lumican, and their GAG chain-synthesizing enzymes are regulated in myocardial remodeling and reverse remodeling in the mouse

Abstract

On the basis of the role of small, leucine-rich proteoglycans (SLRPs) in fibrogenesis and inflammation, we hypothesized that they could be involved in cardiac remodeling and reverse remodeling as occurs during aortic stenosis and after aortic valve replacement. Thus, in a well-characterized aortic banding-debanding mouse model, we examined the SLRPs decorin and lumican and enzymes responsible for synthesis of their glycosaminoglycan (GAG) chains. Four weeks after banding of the ascending aorta, mice were subjected to a debanding operation (DB) and were subsequently followed for 3 or 14 days. Sham-operated mice served as controls. Western blotting revealed a 2.5-fold increase in the protein levels of glycosylated decorin in mice with left ventricular pressure overload after aortic banding (AB) with a gradual decrease after DB. Interestingly, protein levels of three key enzymes responsible for decorin GAG chain synthesis were also increased after AB, two of them gradually declining after DB. The inflammatory chemokine (C-X-C motif) ligand 16 (CXCL16) was increased after AB but was not significantly altered following DB. In cardiac fibroblasts CXCL16 increased the expression of the GAG-synthesizing enzyme chondroitin polymerizing factor (CHPF). The protein levels of lumican core protein with N-linked oligosaccharides increased by sevenfold after AB and decreased again 14 days after DB. Lumican with keratan sulfate chains was not regulated. In conclusion, this study shows alterations in glycosylated decorin and lumican core protein that might be implicated in myocardial remodeling and reverse remodeling, with a potential important role for CS/DS GAG chain-synthesizing enzymes.