Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging
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 10(11) 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 (99m)Tc-labeled RGD peptide (NC100692, GE Healthcare) was used to assess temporal and regional alpha(v) integrin activation. Rats were injected with NC100692 followed by (201)Tl 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 alpha(v) integrin was observed in IGF-1 rats at 4 weeks after 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 alpha(v) integrin activation which is linked to angiogenesis. MicroSPECT-CT imaging with (99m)Tc-NC100692 and quantitative GWC successfully assessed differences in alpha(v) integrin activation between IGF-1-treated and control animals post-MI. (c) 2009. Published by Elsevier Ltd. All rights reserved.
Dobrucki LW, Tsutsumi Y, Kalinowski L, Dean J, Gavin M, Sen S, Mendizabal M, Sinusas AJ, Aikawa R. Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging J Mol Cell Cardiol 2010 Jun;48(6):1071-9.