Diabetes Mellitus Promotes Atrial Structural Remodeling and PARP-1/Ikkα/NF-κB Pathway Activation in Mice

Abstract

Tianyu Meng,1,* Jie Wang,2,3,* Manyun Tang,2 Shangyu Liu,4 Ligang Ding,4 Yang Yan5 1Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 4Clinical EP Lab & Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 5Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang DingClinical EP Lab & Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaEmail [email protected] YanDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Diabetes mellitus (DM) has been demonstrated to be linked to atrial fibrillation (AF). However, the underlying mechanisms of the DM-associated increase in AF susceptibility and the potential effects of DM on atrial remodeling remain unclear.Methods and Results: Twenty-five C57BL/6 mice were randomly assigned to the normal/control group (Con, n=10) and model group (n=15). Mice in the model group were administered a high-fat diet combined with multiple injections of low-dose streptozocin (STZ) (35 mg/kg). Eleven mice were ultimately included in DM group. Left atrial tissue structural and inflammatory alterations were assessed. In our study, the atrial weights of DM mice were markedly heavier than those of mice in the Con group. DM mice exhibited significantly increased fasting plasma glucose, fasting insulin, and dyslipidaemia. Furthermore, H&E and Masson’s staining revealed broadened interstitial spaces, myocyte disarray and atrial fibrosis in DM mice. The expression levels of the atrial inflammation-associated factor nuclear factor κB (NF-κB) and its pathway were significantly altered in the atria of DM mice.Conclusion: DM could induce atrial structural remodeling and inflammation in mice.Keywords: diabetes mellitus, inflammation, atrial remodeling, PARP-1, NF-κB

Keywords

• diabetes mellitus
• inflammation
• atrial remodeling
• nf-κb
• nlrp3