Adenovirus-mediated overexpression of sST2 attenuates cardiac injury in the rat with severe acute pancreatitis

Abstract Aims Severe acute pancreatitis (SAP) is a serious disease associated with systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been demonstrated to exert immune-regulatory and anti-inflammatory properties in several inflammation-related diseases. In this study, we investigated whether transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate-induced SAP and associated cardiac injury. Main methods A rat model of SAP was induced by retrograde injection of 5% sodium taurocholate (1 ml/kg) into the biliopancreatic duct. Rats in the treatment groups were intravenously injected with adenovirus expressing sST2 (Ad-sST2, 1 × 10 9 particles/rat) or green fluorescent protein (Ad-GFP) via the tail vein 48 h before SAP induction. Histological changes in the pancreatic and heart tissues, and parameters for evaluating SAP and associated cardiac injury were determined at 24 h after SAP. Key findings Sodium taurocholate induced obvious pathological changes in pancreas and elevated serum levels of amylase and lipase. Furthermore, SAP animals exhibited significant cardiac impairment, evidenced by decreased cardiac function, increased myocardial apoptosis and cardiac-related enzymes including creatine kinase isoenzyme, lactate dehydrogenase, and Troponin T. Administration of Ad-sST2 markedly improved the structure of pancreas and heart tissues, and reversed the alterations in serum amylase, lipase and cardiac-related enzymes. In addition, Ad-sST2 treatment downregulated pro-inflammatory cytokines production, demonstrating the anti-inflammatory property of sST2. Significance Our results suggest that administration of Ad-sST2 significantly attenuated the severity of SAP and associated cardiac damage, and the cardioprotective effect is associated with its anti-inflammatory action.