Angiotensin-(1–7) Restores Microcirculation Profiles in Acute Pancreatitis

Abstract

The aim of this study was to investigate whether angiotensin (Ang)-(1-7)-mediated restoration of pancreatic microcirculation profiles and endothelial injury is associated with the expression of telomerase reverse transcriptase (TERT). Wild-type, TERT transgene, and TERT knockdown mice were used in this study, and acute pancreatitis model was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS). Pancreatitis was confirmed by histopathology and serum amylase levels. Pancreatic microcirculation function was assessed by laser Doppler. Endothelial injury model was established by exposing endothelial cells to LPS. Proinflammatory cytokines were detected using enzyme-linked immunosorbent assay, endothelial permeability was detected using transwell assay, and mitochondrial dysfunction and mitochondrial reactive oxygen species (mtROS) were determined by performing confocal microscopy. The effects of Ang-(1-7) in the treatment of pancreatic microcirculation dysfunction were associated with TERT expression. In addition, Ang-(1-7) protected against endothelial cell lesions via inhibiting the increase in endothelial cell permeability and release of proinflammatory cytokines in a TERT-dependent manner. Furthermore, TERT was involved in Ang-(1-7)-mediated attenuation of mitochondrial dysfunction and mtROS in LPS-induced endothelial cells. Angiotensin-(1-7) restores pancreatic microcirculation profiles and reverses endothelial injury by inhibiting mtROS production and mitochondrial dysfunction in a TERT-dependent manner.