Syndecan-4 shedding is involved in the oxidative stress and inflammatory responses in left atrial tissue with valvular atrial fibrillation.

Oxidative stress and inflammation play critical roles in the development and maintenance of atrial fibrillation (AF). In addition, syndecan-4 (Synd4) shedding induced by oxidative stress or inflammation plays a role in the migration of inflammatory cells. Therefore, we hypothesized that Synd4 shedding was also involved in the inflammatory response in atrial fibrillation patients with valvular heart disease. To confirm this suppose, left atrial appendages and clinical data were obtained from 65 patients with valvular disease undergoing valve surgery. Ten left atrial appendages obtained from healthy heart donors were used as controls. Analyses including histopathology, western blotting, and enzyme kinetics were performed to assess the oxidative injury, inflammation responses, and Synd4 shedding. The results showed that the inflammatory response and oxidative injury were increased significantly, whereas as levels of the Synd4 ectodomain was decreased significantly in AF patients. Furthermore, Synd4 ectodomain levels were correlated with atrial oxidative and inflammatory markers. The results showed that Synd4 shedding is a molecular pathological alteration in the development and maintenance of inflammation-associated AF.