Heparan sulfate potentiates leukocyte adhesion on cardiac fibroblast by enhancing Vcam-1 and Icam-1 expression.

Unlabelled: Cardiac fibroblasts (CF) act as sentinel cells responding to chemokines, cytokines and growth factors released in cardiac tissue in cardiac injury events, such as myocardial infarction (MI). Cardiac injury involves the release of various damage-associated molecular patterns (DAMPs) including heparan sulfate (HS), a constituent of the extracellular matrix (ECM), through the TLR4 receptor activation triggering a strong inflammatory response, inducing leukocytes recruitment. This latter cells are responsible of clearing cell debris and releasing cytokines that promote CF differentiation to myofibroblast (CMF), thus initiating scar formation.

Lipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation.

Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-β1 (TGF-β1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-β1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-β1 is antagonized by LPS and the mechanism involved.