Angiotensin-(1-7) protects cardiomyocytes against the high glucose-induced injury by inhibiting ROS-activated Cox-2 pathway

Objective To investinate the roles of reactive oxygen species(ROS)-activated cyclooxygenase-2(COX-2) in high glucose(HG)-induced cardiomyocyte injury and whether Angiotensin-(1-7) [Ang-(1-7)] inhibits the HG-induced injury by modulating the ROS-activated COX-2 pathway in cardiomyocytes.Methods The expression of COX-2 was detected by Western blot assay; Cell viability was measured by cell counter kit(CCK-8); The changes in morphology and amount of apoptotic cells were tested by Hoechst33258 nuclear staining; The intracellular level of ROS was assessed by DCFH-DA staining and photofluorography; The mitochondrial membrane potential(MMP) was analysed by JC-1 staining and photofluorography.Results Co-treatment of H9c2 cariac cells with HG and 1 μmol / L Ang-(1-7) or 1000 μmol / L N-acetyl-L-cysteine(NAC),attenuated up-regulation of COX-2 expression induced by HG.Exposure of the cells to 35 mmol / L glucose(HG) for 24 h induced significant injuries,evidenced by decreases in cell viability and MMP,increases in the number of apoptotic cells and the intracellular level of ROS generation.The co-treatment of the cells with HG and Ang-(1-7) or NS-398(an inhibitor of COX-2) obviously attenuated the HG-induced injuries mentioned above.Conclusion Ang-(1-7)protects cardiomyocytes against the HG-induced injury by inhibiting ROS-activated COX-2 pathway.