Taniyama Yoshiaki, Sanada Fumihiro, Morishita Ryuichi
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine.
Nihon Rinsho. 2010 May;68(5):949-52.
The complications of diabetes mellitus have a significant impact on patient survival and quality of life with respect to ischemic disease. Therapeutic gene therapy was performed for peripheral artery disease (PAD) using vascular endothelial growth factor (VEGF), but VEGF gene therapy in phase III clinical trial for PAD did not succeed. Although hepatocyte growth factor (HGF) is also a potent angiogenic growth factor in animal models of ischemia, their characteristics are not the same in clinical trials. In this background, we demonstrated that HGF, but not VEGF, attenuated angiotensin II-induced senescence of endothelial progenitor cells through a reduction of oxidative stress by inhibition of the phosphatidylinositol-3,4,5-triphosphate/Akt pathway. Therapeutic gene therapy still may improve patients with the complications of diabetes mellitus.
糖尿病并发症对缺血性疾病患者的生存和生活质量有重大影响。使用血管内皮生长因子（VEGF）对周围动脉疾病（PAD）进行了治疗性基因治疗，但针对PAD的III期临床试验中的VEGF基因治疗未成功。尽管肝细胞生长因子（HGF）在缺血动物模型中也是一种有效的血管生成生长因子，但其在临床试验中的特性并不相同。在此背景下，我们证明，HGF而非VEGF通过抑制磷脂酰肌醇-3,4,5-三磷酸/Akt途径减少氧化应激，从而减轻血管紧张素II诱导的内皮祖细胞衰老。治疗性基因治疗仍可能改善糖尿病并发症患者的病情。
