Cardiac Stem Cells Suppressed Cardiac Nerve Sprouting via Attenuated Oxidative Stress in a Rat Model of Myocardial Infarction

Objective: To investigate whether cardiac stem cells (CSCs) can attenuate oxidative stress and improve sympathetic remodeling in rats following myocardial infarction (MI). Methods: Sprague-Dawley rats were randomly divided into three groups: 1) MI with CSCs transplantation (CSCs group, n=15); 2) MI control (Control group, n=15); 3) sham control group (Sham group, n=10). Two weeks after surgery, the animals were subjected to intramyocardial injection. Four weeks after injection, left ventricular function, level of oxidative stress, cardiac nerve sprouting and nerve growth factor (NGF) expression were determined. Results: At 4 weeks after intramyocardial injection, fractional shortening (FS) and left ventricular ejection fraction (LVEF) markedly decreased in CSCs and control groups. However, systolic function were partly preserved in CSCs group compared with control group (P<0.01). The myocardial malondialdehyde (MDA) content, MDA/Superoxide Dismutase (SOD) ratio, NGF expression and density of tyrosine hydroxylase (TH)-positive nerve in peri-infarct zone was significantly increased in the control group and CSCs group than the sham group (all P<0.01). However, all of these valuables were decreased in CSCs group when compared with control group (all P<0.01 except for NGF expression P< 0.05). Furthermore, a positive correlation was observed between the degree of sympathetic remodeling and the level of MDA/SOD ratio (r=0.86, R²=0.75). Conclusion: CSCs suppressed sympathetic remodeling after MI probably via attenuated oxidative stress and downregulated NGF expression, which in turn leads to a promising treatment for SCD post MI.