Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes.
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.
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Yong
Y
Zhao
Shandong Medicinal Imaging Research Institute, Jinan 250021, China.
Guo-Ming
GM
Cui
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Nan-Nan
NN
Zhou
Intensive Care Unit, Shouguang People's Hospital, Weifang 262700, China.
Cong
C
Li
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Qing
Q
Zhang
Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.
Hui
H
Sun
Department of Cardiac Surgery, The 4th Hospital of Jinan, Jinan 250031, China.
Bo
B
Han
Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Cheng-Wei
CW
Zou
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Li-Juan
LJ
Wang
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Xiao-Dong
XD
Li
Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Jian-Chun
JC
Wang
D000328:Adult; D020517:Atrial Appendage / Q000201:enzymology*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D015153:Blotting, Western; D019703:Calcineurin / Q000032:analysis* / Q000235:genetics; D002154:Calpain / Q000032:analysis* / Q000235:genetics; D048909:Diabetes Complications / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D005260:Female; D006349:Heart Valve Diseases / Q000150:complications* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000032:analysis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human; C494010:NFATC4 protein, human; D019703:Calcineurin; D002154:Calpain; C569870:CAPN2 protein, human