Experimental Hematology Laboratory, Department of Physiology, Xiang-Ya School of Medicine, Central South University, Changsha 410008, China.
Biol Pharm Bull. 2010;33(11):1806-13. doi: 10.1248/bpb.33.1806.
Endothelial dysfunction/loss is a key event in the development of vascular diseases, including native atherosclerosis (AS). Recent studies have shown that endothelial progenitor cells (EPCs) have the ability to repair endothelial cells that have been lost or damaged following AS. As a result, the therapy of transplanting EPCs is a promising option for the treatment of AS. However, the therapeutic effect on AS with only EPCs transplantation has not been satisfactory. The upregulation of those genes, which prevent the progress of AS in EPCs, is a novel therapeutic strategy for AS. Because it can reduce macrophage foam cell formation and protect endothelial cells from the oxidation of low-density lipoprotein (ox-LDL), paraoxonase-1 (PON1) gene is a candidate for gene therapy in AS. In this study, a recombinant adeno-associated virus (rAAV) vector carrying the human paraoxonase-1 (hPON1) gene (rAAV-PON1) was constructed, and endothelial progenitor cells (EPCs) transfected with rAAV-PON1 were transplanted into the atherosclerosis model of Sprague-Dawley rats (SD rats). The results of doppler ultrasound and histological analysis showed that the group transplanted with the hPON1 gene-transfected EPCs was superior to the group transplanted only with the EPCs and was also better than the group with hPON1 gene injection alone. The results indicated that rAAV-mediated hPON1 gene-transfected EPCs is a potentially valuable new tool in the treatment of atherosclerosis.
内皮功能障碍/丧失是血管疾病发展的一个关键事件，包括原发性动脉粥样硬化（AS）。最近的研究表明，内皮祖细胞（EPCs）具有修复 AS 后丢失或受损的内皮细胞的能力。因此，移植 EPCs 的治疗是治疗 AS 的一种有前途的选择。然而，仅通过 EPCs 移植治疗 AS 的效果并不令人满意。上调那些可防止 EPCs 中 AS 进展的基因是 AS 的一种新的治疗策略。由于它可以减少巨噬细胞泡沫细胞的形成，并保护内皮细胞免受低密度脂蛋白（ox-LDL）的氧化，因此对氧磷酶 1（PON1）基因是 AS 基因治疗的候选基因。在这项研究中，构建了携带人对氧磷酶 1（hPON1）基因的重组腺相关病毒（rAAV）载体（rAAV-PON1），并将 rAAV-PON1 转染的内皮祖细胞（EPCs）移植到 Sprague-Dawley 大鼠（SD 大鼠）的动脉粥样硬化模型中。多普勒超声和组织学分析的结果表明，移植 hPON1 基因转染的 EPCs 的组优于仅移植 EPCs 的组，也优于单独注射 hPON1 基因的组。结果表明，rAAV 介导的 hPON1 基因转染的 EPCs 是治疗动脉粥样硬化的一种有潜在价值的新工具。
