Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes
作者
Zhao, Y;Cui, GM;Zhou, NN;Li, C;Zhang, Q;Sun, H;Han, B;Zou, CW;Wang, LJ;Li, XD;Wang, JC
作者单位
[Zhao, Yong; Zhou, Nan-nan; Zhang, Qing; Wang, Li-juan; Li, Xiao-dong; Wang, Jian-chun] Shandong Univ, Shandong Prov Hosp Affiliated, Dept Geriatr Cardiol, Jinan 250021, Peoples R China.;-;[Cui, Guo-ming] Shandong Med Imaging Res Inst, Jinan 250021, Peoples R China.;-;[Li, Cong] Shouguang Peoples Hosp, Intens Care Unit, Weifang 262700, Peoples R China.;-;[Sun, Hui] Shandong Univ, Jinan Cent Hosp Affiliated, Dept Cardiol, Jinan 250013, Shandong, Peoples R China.;-;[Han, Bo] 4th Hosp Jinan, Dept Cardiac Surg, Jinan 250031, Peoples R China.;-;[Zou, Cheng-wei] Shandong Univ, Shandong Prov Hosp, Dept Cardiac Surg, Jinan 250021, Peoples R China.
摘要
Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha-and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes.
关键词
ACTIVATION; HYPERTROPHY; FAILURE; PROTEOLYSIS; MYOCARDIUM; PROGNOSIS; PATHWAY
基本信息
