Osteoglycin (OGN) modulates inflammation during viral myocarditis via an interaction with Toll Like Receptor 4.

Background Small leucine rich proteoglycans, like OGN, present in the extracellular matrix, have been described to interact with collagen and soluble growth factors, thereby modifying the extracellular milieu. Not much is known however about their influence on inflammation, therefore we investigated the role of OGN in viral myocarditis. Results In both humans and mice with viral myocarditis, we demonstrated increased expression of OGN. We showed distinct OGN protein footprints in different murine cardiovascular disease models, with, a of 72kDa variant most abundant in viral myocarditis. After treatment with chondroitinase ABC there was a shift in detected size indicating the attachment of chondroitin sulfate to OGN. The 72kDa OGN co‐immunoprecipitated with TLR4. Lastly, stimulation of bone marrow derived macrophages with LPS demonstrated a decrease in cytokine production, in the presence of OGN. Conclusion We demonstrated for the first time that variants of OGN are present in different cardiomyopathies. We showed that the OGN variant abundant in viral myocarditis had the glycosaminoglycan chondroitin sulfate attached to it, and that this variant bound to TLR4, hence modulate the response of macrophages to LPS. Understanding this mechanism and identifying the biochemical substrates responsible for this interaction, could lead to much needed new therapies for viral myocarditis.