Abstract
Metformin serves an important role in improving the functions of endothelial progenitor cells (EPCs). MicroRNAs (miRNAs), small non‑coding RNAs, have been investigated as significant regulators of EPC vascular functions. The present study investigated the molecular crosstalk between metformin and miRNA‑130a (miR‑130a) in the functions of EPCs exposed to palmitic acid (PA). Isolated EPCs were treated with metformin, PA, and metformin + PA, respectively. Cell Counting Kit‑8, Transwell and Matrigel assays were performed to detect the proliferation, migration and tube formation ability of EPCs following different treatments. The expression of miR‑130a, phosphatase and tensin homolog (PTEN) and phosphorylated‑AKT was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting. The specific mechanism underlying the function of metformin in EPCs was further elucidated by transfecting miR‑130a mimics and inhibitor to overexpress and inhibit the expression of miR‑130a in EPCs, respectively. EPCs exhibited impaired functions of proliferation (P<0.01 compared with the control), migration (P<0.01 compared with the control) and tube formation (P<0.01 compared with the control) following treatment with PA, and the expression levels of miR‑130a and PTEN were decreased and increased, respectively. However, the presence of metformin, or the overexpression of miR‑130a using miR‑130a mimic alleviated the impairment of angiogenesis and proliferation, decreased the expression of PTEN and activated the phosphoinositide‑3 kinase/AKT pathway in EPCs exposed to PA. By contrast, downregulating the expression of miR‑130a with a miR‑130a inhibitor reversed the metformin‑mediated protection. These results demonstrate the beneficial effect of miR‑130a/PTEN on EPC functions, which can be regulated by metformin. The effects of metformin on improving PA‑induced EPC dysfunction are mediated by miR‑130a and PTEN, which may assist in the prevention and/or treatment of diabetic vascular disease.