BACKGROUND: Endothelial progenitor cells are characterized by proliferation, migration and the ability to differentiate into endothelial cells and play an important role in the occurrence and development of coronary arteriosclerotic heart disease and diabetes mellitus and their complications.
OBJECTIVE: To investigate the effects of selective peroxisome proliferative activated receptor γ excitomotor pioglitazone on the proliferation of rat bone marrow endothelial progenitor cells and the underlying mechanisms.
METHODS: Using density gradient centrifugation and differential adherence methods, rat bone marrow endothelial progenitor cells were cultured in culture medium containing 0, 1, 10, 50, 100, 200 μmol/L pioglitazone and the optimal concentration of pioglitazone in promoting the proliferation of endothelial progenitor cells was determined. The endothelial progenitor cells cultured for 7 days were randomly divided into five groups: control group (dimethyl sulfoxide), pioglitazone group (50 μmol/L pioglitazone), peroxisome proliferative activated receptor γ antagon group (50 μmol/L pioglitazone+10 μmol/L peroxisome proliferative activated receptor γ antagon GW9662), phosphatidylinositol 3-kinase/Akt blocker group (50 μmol/L pioglitazone+50 μmol/L phosphatidylinositol 3-kinase/protein kinase B channel blocker Wortmannin), extracellular regulated protein kinase blocker group (50 μmol/L pioglitazone+20 μmol/L extracellular regulated protein kinase blocker PD98059). The proliferation of endothelial progenitor cells in each group was observed.
RESULTS AND CONCLUSION: Through the inverted microscopy, cell proliferation was not obvious in the first 4 days of culture, peaked during 5-10 days, showing colony-forming units and line-like structure, and reached 80% confluency at 10 days. After 7 days of culture, endothelial progenitor cells could swallow DiL-ac-LDL and FITC-europaeus agglutinin-1. 10-200 μmol/L, particularly 50 μmol/L, pioglitazone could significantly promote the proliferation of endothelial progenitor cells (P < 0.01). Wortmannin and GW9662 could greatly antagonize pioglitazone promotion of cell proliferation, while PD98059 had no effects on the effects of pioglitazone. These findings suggest that pioglitazone promotes the proliferation of rat bone marrow endothelial progenitor cells via phosphatidylinositol 3-kinase/protein kinase B signaling pathway.