Effect of adenovirus mediated β2-AR overexpression on IL-10 level secreted by cardiomyocytes of heart failure rats

Abstract

The effect of β2-adrenergic receptor (AR) overexpression on interleukin (IL)-10 content secreted by cardiomyocytes of heart failure (HF) rats was investigated. A rat model of chronic HF was established by partially banding abdominal aorta and the cardiomyocytes were isolated with collagenase II. The cardiomyocytes were then transfected with adenovirus type 5-ADRβ2-enhanced green fluorescent protein (EGFP) for 48 h to observe the changes of β2-AR protein expression using western blot analysis. The IL-10 level was detected by ELISA. The experiment was divided into seven groups: Control, HF, HF+EGFP, HF+β2, sham, sham+EGFP and sham+β2 groups. Compared with the sham-operated group, left ventricular diastolic dimension, and left ventricular systolic dimension were increased (P<0.05), whereas ejection fraction and fractional shortening were decreased (P<0.05) in the HF group. Compared with the sham group, the cardiomyocyte survival rate of the HF group was significantly reduced (P<0.05). Compared with the control or sham group, the β2-AR protein level of the HF group showed no significant differences (P>0.05). Compared with the HF and HF+EGFP groups, the expression of β2-AR protein of cardiomyocytes was increased in the HF+β2 group (P<0.05). Compared with the sham group, IL-10 content secreted by cardiomyocytes in the HF group was increased (P<0.05). Compared with the HF and HF+EGFP groups, IL-10 content in the HF+β2 group was increased significantly (P<0.05). In conclusion, the concentration of IL-10 secreted by cardiomyocytes of HF rats was increased. The overexpression of β2-AR in the cardiomyocytes of HF rats was able to enhance the secretion of IL-10.

Protective transcriptional mechanisms in cardiomyocytes and cardiac fibroblasts

“…Gene programs that facilitate the protective PI3K/Akt and nitric oxide/PKG pathways can be modulated by nuclear β-ARs [113,114]. Adenoviral mediated delivery of β2-AR to CMs can increase the expression of the anti-inflammatory cytokine IL-10 following aortic constriction [115]. β2-AR stimulation also increases the expression of the soluble inhibitory binding protein of IL-18, limiting pathological hypertrophy of the myocardium [116].…”