Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model.
Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model.
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血管生成因子 AGGF1 促进小鼠肢体缺血模型中的治疗性血管生成
DOI：
10.1371/journal.pone.0046998
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Lu Q;Yao Y;Yao Y;Liu S;Huang Y;Lu S;Bai Y;Zhou B;Xu Y;Li L;Wang N;Wang L;Zhang J;Cheng X;Qin G;Ma W;Xu C;Tu X;Wang Q
研究背景外周动脉疾病（peripheral arterial disease，PAD）是一种常见病，约占成年人口的12%，发病率和死亡率高。使用血管生成因子的治疗性血管生成被认为是PAD患者的潜在治疗选择。在这项研究中，我们评估了一种新的血管生成因子AGGF 1在PAD小鼠严重肢体缺血模型中治疗血管生成的潜力。方法和结果通过结扎小鼠右侧髂总动脉和股动脉建立单侧后肢缺血模型。与注射空载体的对照小鼠（对照组）相比，肌内给予人AGGF 1表达质粒的DNA的缺血小鼠（AGGF 1组）在给药后导致AGGF 1 mRNA和蛋白质的表达增加。彩色PW多普勒超声心动图显示，在DNA给药后7、14和28天的时间点，AGGF 1组的缺血后肢血流量与对照组相比显著增加（n = 9/组，分别为P = 0.049、0.001和0.001）。 与注射空载体的对照组织相比，AGGF 1组中血流量增加与注射AGGF 1 DNA的肌肉组织中CD 31阳性血管密度增加和坏死减少相关。与对照组相比，AGGF 1组的行走障碍显著减少（P = 0.004）。 AGGF 1的作用呈剂量依赖性。在基因转移后第28天，AGGF 1在增加血流量方面明显优于FGF-2（P = 0.034），尽管在组织坏死和行走障碍方面没有发现差异。 结论AGGF 1可作为治疗PAD的血管新生候选药物。
Background Peripheral arterial disease (PAD) is a common disease accounting for about 12% of the adult population, and causes significant morbidity and mortality. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD. Methods and Results We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 (AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice with injection of the empty vector (control group). Color PW Doppler echocardiography showed that the blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration (n = 9/group, P = 0.049, 0.001, and 0.001, respectively). Increased blood flow in the AGGF1 group was correlated to increased density of CD31-positive vessels and decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. Ambulatory impairment was significantly reduced in the AGGF1 group compared to the control group (P = 0.004). The effect of AGGF1 was dose-dependent. At day 28 after gene transfer, AGGF1 was significantly better in increasing blood flow than FGF-2 (P = 0.034), although no difference was found for tissue necrosis and ambulatory impairment. Conclusions These data establish AGGF1 as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.
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影响因子：
24
作者：
Rooke TW;Hirsch AT;Misra S;Sidawy AN;Beckman JA;Findeiss LK;Golzarian J;Gornik HL;Halperin JL;Jaff MR;Moneta GL;Olin JW;Stanley JC;White CJ;White JV;Zierler RE;Society for Cardiovascular Angiography and Interventions;Society of Interventional Radiology;Society for Vascular Medicine;Society for Vascular Surgery
通讯作者：
Society for Vascular Surgery
影响因子：
64.8
作者：
Tian, XL;Kadaba, R;Wang, Q
通讯作者：
Wang, Q
影响因子：
39.2
作者：
Baumgartner, I;Rauh, G;Isner, JM
通讯作者：
Isner, JM
影响因子：
3.5
作者：
Dieter, RS;Tomasson, J;McBride, PE
通讯作者：
McBride, PE
影响因子：
8.9
作者：
Olin, Jeffrey W.;Sealove, Brett A.
通讯作者：
Sealove, Brett A.