In vivo imaging of myocardial cell death using a peptide probe and assessment of long-term heart function

Bodhraj Acharya, Kai Wang, In-San Kim, Woongchol Kang, Chanil Moon, Byung Heon Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

During acute myocardial infarction (AMI), both apoptosis and necrosis of myocardial cells could occur and lead to left ventricular (LV) functional decline. Here we determined whether in vivo imaging signals of myocardial cell death by ApoPep-1 (CQRPPR), a peptide probe that binds to apoptotic and necrotic cells through histone H1, at an early stage after AMI showed correlation with the long-term heart function. AMI was induced using a rat model of ischemia and reperfusion (I/R) injury. Fluorescence-labeled ApoPep-1 was administered by intravenous injection into rats 2 h after reperfusion. Ex vivo imaging of hearts isolated 2 h after peptide injection showed higher levels of near-infrared fluorescence (NIRF) signals at hearts of I/R rats than those of sham-operated rats. The fluorescent peptide was rapidly cleared from the blood and did not bind to red and white blood cells. Localization of fluorescent ApoPep-1 at the area of cell death was demonstrated by co-staining of myocardial tissue with TUNEL. The intensity of in vivo NIRF imaging signals by homing of ApoPep-1 to injured myocardium of I/R rats obtained 2 h after peptide injection (equivalent to 4 h after injury) showed strong and moderate correlation with the change in the LV ejection fractions (r2 = 0.82) and the size of the fibrotic area (r2 = 0.64), respectively, observed at four weeks after injury. These results suggest that ApoPep-1-mediated in vivo imaging signals of myocardial cell death, including both apoptosis and necrosis, at an early stage of AMI could be a potential biomarker for assessment of long-term outcome of heart function.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalJournal of Controlled Release
Volume172
Issue number1
DOIs
Publication statusPublished - 2013 Oct 1
Externally publishedYes

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Keywords

  • In vivo imaging
  • Ischemia and reperfusion injury
  • Myocardial cell death
  • Peptide probe

ASJC Scopus subject areas

  • Pharmaceutical Science

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