Khurrum Shahzad, Ihsan Gadi, Sumra Nazir, Moh'd Mohanad Al-Dabet, Shrey Kohli, Fabian Bock, Lukas Breitenstein, Satish Ranjan, Tina Fuchs, Zuhir Halloul, Peter P Nawroth, Pier Giuseppe Pelicci, Ruediger C Braun-Dullaeus, Eric Camerer, Charles T Esmon, Berend Isermann
Impaired activated protein C (aPC) generation is associated with atherosclerosis and diabetes mellitus. Diabetes-associated atherosclerosis is characterized by the hyperglycaemic memory, e.g., failure of disease improvement despite attenuation of hyperglycaemia. Therapies reversing the hyperglycaemic memory are lacking. Here we demonstrate that hyperglycaemia, but not hyperlipidaemia, induces the redox-regulator p66Shc and reactive oxygen species (ROS) in macrophages. p66Shc expression, ROS generation, and a pro-atherogenic phenotype are sustained despite restoring normoglycemic conditions...
2018: Communications Biology