Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging

Lawrence W. Dobrucki, Yoshiaki Tsutsumi, Leszek Kalinowski, Jarrod Dean, Mary Gavin, Sabyasachi Sen, Marivi Mendizabal, Albert J. Sinusas, Ryuichi Aikawa

Research output: Contribution to journalArticlepeer-review

Abstract

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 16weeks 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 16weeks post-MI. Significantly higher activation of αv integrin was observed in IGF-1 rats at 4weeks after treatment compared with control group, although the activation was lower in the IGF-1 group at 16weeks. 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.

Original languageEnglish (US)
Pages (from-to)1071-1079
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume48
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • AAV
  • Angiogenesis
  • IGF-1
  • MicroSPECT-CT
  • Molecular imaging
  • Myocardial infarction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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