The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis

Figure 1

Model of proinflammatory response induced by heparanase. Heparanase cleaves and solubilizes heparan sulfate (HS) fragments from their proteoglycan (HSPG) within highly sulfated regions. Analogue to LPS, HS fragments then signal through MyD88-dependent receptors, of which TLR-4 is one, and this leads to NF-kappaB cleavage and activation. NF-kappaB-dependent upregulation leads to the release of cytokine production including interleukin-6 (IL-6). Cytokines are involved in activating heparanase, thereby enhancing the devastating circle of an inflammatory response.