Bhang Suk H, Kim Ju H, Yang Hee S, La Wan-Geun, Lee Tae-Jin, Sun Ah-Young, Kim Ga H, Lee Minhyung, Kim Byung-Soo
School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-744, Republic of Korea.
Biomaterials. 2009 Oct;30(31):6247-56. doi: 10.1016/j.biomaterials.2009.07.058. Epub 2009 Aug 14.
Ectopic expression of heme oxygenase-1 (HO-1) in ischemic tissue protects the tissue from apoptosis and necrosis and promotes angiogenesis. However, apoptosis and necrosis will decrease HO-1 gene transfection efficacy. We hypothesized that fibroblast growth factor-2 (FGF2) would attenuate ischemic damage during the incipient period, improve HO-1 gene transfection and, in turn, enhance neovascularization. To test this hypothesis, we employed a mouse model of hindlimb ischemia and treated the mice with HO-1 gene therapy alone, FGF2 alone, or HO-1 gene therapy plus FGF2. As controls, a group of mice was left untreated. At 12h, prior to the expression of exogenously delivered HO-1, apoptosis was significantly reduced in mice treated with FGF2, either alone or in combination with HO-1 gene therapy. At 3 days, HO-1 expression was greater in mice that also received FGF2 than in mice treated with HO-1 gene therapy alone. The expression of angiogenic growth factors and angiogenesis was greater in mice treated with HO-1 gene therapy plus FGF2 than in mice treated with HO-1 gene therapy alone. These data indicate that FGF2 rescued muscle necrosis prior to the exogenous expression of HO-1 and enhanced HO-1 gene transfection in ischemic murine limbs.
