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. doi: 10.1016/j.yjmcc.2009.10.008. Epub 2009 Oct 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus / genetics
  • Gene Expression Regulation*
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis*
  • Integrin alphaV / metabolism
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Neovascularization, Pathologic*
  • Oligopeptides / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Technetium / pharmacology
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Tomography, X-Ray Computed / methods*


  • Integrin alphaV
  • Oligopeptides
  • Insulin-Like Growth Factor I
  • Technetium
  • arginyl-glycyl-aspartic acid