Number and function impairment of resident C-Kit+ cardiac stem cells in mice with renal dysfunction caused by 5/6 nephrectomy

Abstract

Background: Cardiac stem cell (CSC) dysfunction exists in various kinds of cardiovascular diseases, and may be responsible for the insufficient regeneration of cardiac myocytes and coronary vessels. However, whether chronic renal failure (CRF) affected CSC is unknown. Method: CRF was induced in adult male mice by 5/6 nephrectomy. The mice were killed at 12 weeks after operation. C-kit+ CSC numbers was evaluated by flow cytometer. Apoptosis and DNA damage of C-kit+ CSC in the control and CRF mice was analyzed by immunohistochemistry. In the in vitro study, normal medium, and medium with uremic rat serum were used for the CSC culture. Results: CSC counts attenuated significantly in the chronic renal failure model, whereas apoptosis cells and 8-OHdG-positive cells significantly increased. CSC derived form 5/6 nephrectomy mice showed an impaired anti-oxidant potential. In the cultured cells, CSCs subjected to uremic rat serum showed a higher frequency of TUNEL stain-positive and 8-OHdG-positive cells. The uremia rat serum reduced the expression of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in CSC. Conclusions: The current study elucidated that CSC number and function disorders existed in mice with chronic renal insufficiency. Apoptosis, oxidative stress and reduced angiogenic factors secretion caused by uremic toxins in serum are contributors to CSC dysfunction.