Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation.
Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation.
复制标题
在后肢缺血模型中，灌注和血管生成增加，其质粒FGF-2通过非侵入性电穿孔传递。
作者：
提供成纤维细胞生长因子-2（FGF-2）的基因治疗方法已显示出作为增加缺血肢体血流的潜在治疗方法的前景。目前，递送编码治疗目的基因（如FGF-2）的质粒的有效非侵入性技术有限。我们试图确定皮内注射编码FGF-2（pFGF）的质粒DNA，然后进行非侵入性皮肤电穿孔（pFGFE+）是否可以增加后肢缺血大鼠模型的血流量和血管生成。在术后第0天给予pFGFE+或对照治疗。与单独注射pFGF（pFGFE-）相比，递送pFGFE+显著增加FGF-2表达10天。此外，从术后第3天开始，通过激光多普勒灌注成像测量，pFGFE+的FGF-2表达的增加足以显著增加缺血肢体血流。pFGFE+治疗组的缺血肢体血流量在研究终点（术后第14天）时仍显著高于所有对照组。腓肠肌横截面的免疫组织化学染色确定在pFGFE+处理组中毛细血管密度增加两倍。我们的研究结果表明，pFGFE+是一种潜在的非侵入性，非病毒的治疗方法，以增加灌注和血管生成治疗肢体缺血。
Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective non-invasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by non-invasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the increase in FGF-2 expression with pFGFE+ was sufficient to significantly increase ischemic limb blood flow, measured by laser Doppler perfusion imaging, beginning on postoperative day 3. Ischemic limb blood flow in the pFGFE+ treatment group remained significantly higher than all control groups through the end point of the study, postoperative day 14. Immunohistochemical staining of gastrocnemius cross-sections determined there was a two-fold increase in capillary density in the pFGFE+ treatment group. Our results suggest that pFGFE+ is a potential non-invasive, non-viral therapeutic approach to increase perfusion and angiogenesis for the treatment of limb ischemia.
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影响因子：
4.2
作者：
Heller, Richard;Cruz, Yolmari;Jaroszeski, Mark J.
通讯作者：
Jaroszeski, Mark J.
影响因子：
6.5
作者：
Lee, PY;Chesnoy, S;Huang, L
通讯作者：
Huang, L
影响因子：
5.3
作者：
Fujii, Takaaki;Yonemitsu, Yoshikazu;Sueishi, Katsuo
通讯作者：
Sueishi, Katsuo
DOI：
10.1016/s0735-1097(00)00882-2
发表时间：
2000-10-01
影响因子：
24
作者：
Lazarous, DF;Unger, EF;Quyyumi, AA
通讯作者：
Quyyumi, AA
影响因子：
12.4
作者：
Glasspool-Malone, J;Somiari, S;Malone, RW
通讯作者：
Malone, RW