Heart failure & cardiomyopathies
Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling
Authors' conclusion
CS glycosaminoglycans accumulate during cardiac pathological remodeling and mediate myocardial inflammation and fibrosis.
Study context
- Population
- Failing human hearts and rat models of pathological cardiac remodeling (transverse aortic constriction or isoprenaline infusion)
- Comparison
- Recombinant human arylsulfatase B (rhASB) vs no treatment in rat models of pathological remodeling
Main finding
As reported in the abstract
- Failing human hearts: significant perivascular and interstitial chondroitin sulfate (CS) accumulation, particularly in regions of intense fibrosis
- Relative composition of CS disaccharides unchanged
- TGF-β induced CS upregulation in cardiac fibroblasts
- CS accumulation also in rat pressure-overload and isoprenaline models
- rhASB (early in TAC model, delayed in isoprenaline model) prevented cardiac deterioration and augmented functional recovery, with reduced myocardial inflammation and overall fibrosis
- TNF-α a direct binding partner of CS chains; rhASB reduced TNF-α-induced inflammatory gene activation in endothelial cells and macrophages in vitro
Original publication
Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling. Circulation. Published 25 January 2018. doi:10.
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