Impaired in vitro functions of endothelial progenitor cells from db/db mice.

Type 2 Diabetes Mellitus may lead to severe complications caused by micro- and macroangiopaties. They result from dysfunction of endothelial cells due to chronic hyperglycaemia. It has been shown that endothelial progenitor cells (EPC) may play a vital role in vascular biology, through induction of neovascularization in ischemic tissues or incorporation into injured vessels. Our aim was to check how thiazolidinediones, the insulin-sensitizers, affect functions of EPC isolated from healthy and diabetic mice.

Experiments were performed in the 10-week old wild type and db/db mice. Some diabetic animals were fed with rosiglitazone (10 mg/kg for 14 days), which ameliorated hyperglycaemia. EPC were purified from the bone marrow and cultured in vitro for 7-10 days. Staining of apoptotic cells with Annexin-V demonstrated that EPC isolated from the wild type mice were significantly more resistant to oxidative stress induced by H2O2 than cells isolated from db/db counterparts. Noteworthy, EPC obtained from rosiglitazone-treated diabetic individuals showed a tendency for improved viability after exposure to H2O2. On the other hand, the same treatment did not influence the increased sensitivity of EPC from db/db mice to apoptosis induced by supplementation of culture media with high concentration of glucose (25 mM). Additionally, EPCs from the untreated or rosiglitazone-treated db/db mice displayed significantly reduced migratory capabilities, which could be fully restored by rosiglitazone (10 μM) added in vitro. This effect was PPARγ-dependent, as it was reversed by supplementation of cells with PPARγ antagonist, GW9662.

Thus, rosiglitazone may improve viability and migration of EPC isolated from diabetic mice.