Number And Function Impairment Of Resident C-kit Positive Cardiac Stem Cells In Mice With Renal Dysfunction Caused By5/6Nephrectomy

Background:Cardiac stem cells (CSCs) dysfunction exists in various kinds of cardiovascular diseases, and may be responsible for the insufficient regeneration of cardiac myocytes and coronary vessels.Methods:The experimental groups were as follows:control (n=6), sham-operated (n=18), and5/6nephrectomy (n=18). The mice were killed at12weeks after operation. Blood and heart tissue were collected for the experiment. Identify numbers of c-kit+CSCs in different groups. Detect the percentage of apoptosis cells and DNA oxidative damage cells in5/6Nx mice and sham-operated mice.0.3%H2O2was employed to mimic oxidative stress, as to evaluated tolerance of5/6Nx mice to oxidative stress. In the in vitro study, normal medium, and medium with uremic rat serum were used for the CSC culture.Results:Renal function and cardiac function were measured at12weeks after operation. As expected, the serum level of creatinine and urea nitrogen significantly increased. CSC counts attenuated significantly in the chronic renal failure model, whereas the terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL) stain-positive cells and8-OHdG-positive cells significantly increased. In the cultured cells, the CSCs subjected to uremic rat serum showed a higher frequency of TUNEL stain-positive and8-OHdG-positive cells. The uremia rat serum reduced the expression of hepatocyte growth factor and vascular endothelial growth factor in CSC.Conclusions:The current study elucidated that CSC number and function disorders exist in mice with chronic renal insufficiency. Apoptosis and oxidative stress caused by uremic toxins in serum are contributors to CSC dysfunction.