Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging.
Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging.
复制标题
DOI：
10.1016/j.yjmcc.2009.10.008
复制
发表时间：
2010-06
影响因子：
5
通讯作者：
Aikawa R
中科院分区：
文献类型：
--
作者：
Dobrucki LW;Tsutsumi Y;Kalinowski L;Dean J;Gavin M;Sen S;Mendizabal M;Sinusas AJ;Aikawa R
胰岛素样生长因子-1（IGF-1）在先前的动物研究中已被发现对血管生成具有有利的作用。本研究采用microSPECT-CT技术观察了腺相关病毒（AAV）介导人IGF-1基因转染大鼠梗死心肌后IGF-1对血管生成的长期影响。通过结扎近端前冠状动脉在Sprague-Dawley大鼠中诱导心肌梗塞（MI），并在梗塞周围区域周围注射总共1011个AAV-CMV-LacZ（对照）或IGF-1载体。IGF-1的表达AAV稳定转导心肌梗死后长达16周，免疫组化显示毛细血管密度显着增加。使用99 mTc标记的RGD肽（NC 100692，GE Healthcare）评估时间和区域αv整联蛋白活化。给大鼠注射NC 100692，然后注射201 Tl氯化物，并进行体内microSPECT-CT成像。成像后，切除心脏并切割用于定量γ孔计数（GWC）。在MI后4周和16周，LacZ和IGF-1大鼠的低灌注区域中NC 100692保留显著增加。与对照组相比，在治疗后4周在IGF-1大鼠中观察到αv整合素的活化显著更高，尽管在16周时IGF-1组的活化较低。通过AAV局部递送IGF-1基因可提供持续的转导并改善MI后的心功能。IGF-1表达有助于增强与血管生成相关的αv整合素活化。使用99 mTc-NC 100692和定量GWC的MicroSPECT-CT成像成功评估了MI后IGF-1处理和对照动物之间αv整联蛋白活化的差异。
Insulin-like growth factor-1 (IGF-1) has been found to exert favorable effects on angiogenesis in prior animal studies. This study explored the long-term effect of IGF-1 on angiogenesis using microSPECT-CT in infarcted rat hearts after delivering human IGF-1 gene by adeno-associated virus (AAV). Myocardial infarction (MI) was induced in Sprague-Dawley rats by ligation of the proximal anterior coronary artery and a total of 1011 AAV-CMV-LacZ (control) or IGF-1 vectors were injected around the peri-infarct area. IGF-1 expression by AAV stably transduced heart muscle for up to 16 weeks post-MI and immunohistochemistry revealed a remarkable increase in capillary density. A 99mTc-labeled RGD peptide (NC100692, GE Healthcare) was used to assess temporal and regional αv integrin activation. Rats were injected with NC100692 followed by 201Tl chloride and in vivo microSPECT-CT imaging was performed. After imaging, hearts were excised and cut for quantitative gamma-well counting (GWC). NC100692 retention was significantly increased in hypoperfused regions of both LacZ and IGF-1 rats at 4 and 16 weeks post-MI. Significantly higher activation of αv integrin was observed in IGF-1 rats at 4 weeks post treatment compared with control group, although the activation was lower in the IGF-1 group at 16 weeks. Local IGF-1 gene delivery by AAV can render a sustained transduction and improve cardiac function post-MI. IGF-1 expression contributes to enhanced αv integrin activation which is linked to angiogenesis. MicroSPECT-CT imaging with 99mTc-NC100692 and quantitative GWC successfully assessed differences in αv integrin activation between IGF-1 treated and control animals post-MI.
登录
查看更多内容
影响因子：
4.6
作者：
Horvath, KA;Doukas, J;Fullerton, DA
通讯作者：
Fullerton, DA
影响因子：
15.9
作者：
Meoli, DF;Sadeghi, MM;Sinusas, AJ
通讯作者：
Sinusas, AJ
影响因子：
3.3
作者：
Kalinowski, Leszek;Dobrucki, Lawrence W.;Sinusas, Albert J.
通讯作者：
Sinusas, Albert J.
影响因子：
37.8
作者：
Melo, LG;Agrawal, R;Dzau, VJ
通讯作者：
Dzau, VJ
影响因子：
3.1
作者：
Edwards, David;Jones, Paul;Godden, Vanessa
通讯作者：
Godden, Vanessa