The matricellular proteins thrombospondin‐2, osteonectin and osteoglycin modulate cardiac inflammation, injury and function during viral myocarditis.

Non‐structural matri‐cellular proteins (MCPs) modulate the process of heart failure (HF) by acting on different cardiac cellular compartments. Here, we investigated whether MCPs, including TSP2, SPARC or osteoglycin (OGN), may affect cardiac inflammation. Therefore, TSP‐2, SPARC and OGN‐null animals and their WT littermates were submitted to human Coxsackievirus B3 (CVB3)‐induced myocarditis. Whereas the absence of TSP‐2 or SPARC increased cardiac inflammation, necrosis and overall mortality as compared to WT at 14 days, resulting in systolic dysfunction at 35 days, lack of OGN was protective. Increased cardiac inflammation and injury was caused by decreased activation of the anti‐inflammatory T‐regulatory cells (TSP‐2‐null) and increased trans‐endothelial leukocyte migration (SPARC‐null). Decreased cytokine activation caused less cardiac inflammation in OGN‐null. Finally, over expression of TSP‐2 or SPARC in WT hearts with AAV9‐TSP2 or AdVSPARC significantly reduced cardiac inflammation and injury. In conclusion, whereas increased SPARC or TSP‐2 protect against cardiac necrosis and failure during viral myocarditis, OGN is detrimental.