Background: Recent research suggests that abnormal Ca2+ handling plays a role in the occurrence and maintenance of atrial fibrillation (AF). Therefore, Ca2+ release and ingestion depend on properties of the ryanodine receptor (RyR) and sarcoplasmic reticulum Ca(2+)ATPase2a (SERCA2a). This study aimed to detect whether SERCA2a gene overexpression has a preventive effect on atrial fibrillation caused by rapid pacing right atrium.
Material/Methods: Forty-eight New Zealand white rabbits were randomly divided into a control group, AF group, AAV9/GFP group, and AAV9/SERCA2a group. The right atrium was rapidly paced at 600 beats/min for 30 days after an intraperitoneal injection of an adeno-associated virus expressing the SERCA2a gene and GFP. The AF induction rate and the effective refraction period (ERP) were measured after 0, 4, 8, 12, and 24 h of pacing. Western blot analysis was used to test for the expression of SERCA2a. Changes in atrial tissue structure were observed by H&E staining and electron microscopy.
Results: The AF induction rate was higher in the AF groups than in the AAV9/SERCA2a group at different time points of pacing. After 12 h of pacing, ERP was significantly prolonged in the AAV9/SERCA2a group compared to the AF and AAV9/GFP groups (p < 0.05). SERCA2a protein expression was significantly lower in the AF and AAV9/GFP groups compared to the control group ( p < 0.05), while expression was significantly higher in the AAV9/SERCA2a group than in the AF and AAV9/GFP groups ( p < 0.05). The myocardial structure of the AAV9/SERCA2a group was significantly improved compared with the AF group, indicating that SERCA2a overexpression relieved the structural remodeling of atrial fibrillation.
Conclusions: SERCA2a overexpression is capable of suppressing ERP shortening and AF induced by rapid pacing atrium. SERCA2a gene therapy is expected to be a new anti-atrial fibrillation strategy.
[1]Xinjiang Med Univ, Affiliated Hosp 1, Clin Med Res Inst, Urumqi, Xinjiang, Peoples R China.
[2]Xinjiang Med Univ, Affiliated Hosp 1, Dept Pacing & Electrophysiol, Urumqi, Xinjiang, Peoples R China.
[3]Xinjiang Med Univ, Affiliated Hosp 1, Dept Heart Funct, Urumqi, Xinjiang, Peoples R China.
[4]Shanghai Jiao Tong Univ, Dept Geriatr, Affiliated Peoples Hosp 6, South Campus, Shanghai, Peoples R China.
(8.0+极速模式)