Rosiglitazone Facilitates Angiogenic Progenitor Cell Differentiation Toward Endothelial Lineage

Abstract
Background— Peroxisome proliferator–activated receptor-γ (PPAR-γ) agonists inhibit vascular smooth muscle proliferation and migration and improve endothelial function. It is unknown whether PPAR-γ agonists favorably modulate bone marrow (BM)–derived angiogenic progenitor cells (APCs) to promote endothelial lineage differentiation and early reendothelialization after vascular intervention. Methods and Results— C57/BL6 mice, treated with or without rosiglitazone (8 mg/kg per day), a PPAR-γ agonist, underwent femoral angioplasty. Rosiglitazone treatment attenuated neointimal formation (intima/media ratio: 0.98±0.12 [rosiglitazone] versus 3.1±0.5 [control]; P<0.001; n=10 per group). Using a BM transplantation model, we identified that 58±12% of the cells within the neointima at 4 weeks were derived from the BM. Pure endothelial marker–positive, pure α-smooth muscle actin (αSMA)–positive, or double-positive APCs could be found both in mouse BM and in human peripheral blood after culture in conditional medium e...