关键词: 骨髓间充质干细胞, 心肌梗死, 红素氧合酶-1, 血管再生

Abstract: Objective: Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with diverse cytoprotective effects, and is reported a role for angiogenesis rencently. We investigated whether HO-1 transduced by MSCs can induce angiogenic effects in infracted myocardium. Methods HO-1 was transfected into cultured MSCs using an adenoviral vector. 1×106 Ad-HO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was respectively injected into rat hearts 1 h intramyocardially after myocardial infarction. Results HO-1-MSCs was able to induce stable expression of HO-1 in Vitro and Vivo. The capillary density and expression of angiogenic growth factors,VEGF and FGF2, were significantly enhanced in HO-1-MSCs-treated hearts compared with Null-MSCs-treated and PBS-treated hearts. However, the angiogenic effects of HO-1 in HO-1-MSCs group could be abolished by treating the animals with HO inhibitor, zinc protoporphyrin. The myocardial apoptosis was marked reduced with significantly reduced fibrotic area in HO-1-MSCs-treated hearts; Furthermore, the cardiac function and remodeling were also significantly improved in HO-1-MSCs-treated hearts than in the other two groups. Conclusion HO-1 modification with MSCs reduces the apoptosis of myocardium and preserves cardiac function and remodeling, and that this is associated with siginficant angiogenesis.

Key words: Mesenchymal stem cells, Myocardial infarction, Heme oxygenase-1, Angiogenesis