title: In vivo imaging of myocardial cell death using a peptide probe and assessment of long-term heart function.
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 2h after reperfusion. Ex vivo imaging of hearts isolated 2h 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 2h after peptide injection (equivalent to 4h after injury) showed strong and moderate correlation with the change in the LV ejection fractions (r(2)=0.82) and the size of the fibrotic area (r(2)=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.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Cell & Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Bodhraj
authors.initials: B
authors.lastname: Acharya
authors.affiliation: Department of Plastic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Cell & Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Gil Hospital, Gachon University, Incheon, Republic of Korea.
authors.forename: WoongChol
authors.initials: W
authors.lastname: Kang
authors.affiliation: Department of Cardiology, School of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address: cmoon351@gmail.com.
authors.forename: Chanil
authors.initials: C
authors.lastname: Moon
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Cell & Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea. Electronic address: leebh@knu.ac.kr.
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000818:Animals; D016923:Cell Death; D015150:Echocardiography, Doppler; D005456:Fluorescent Dyes; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology* / Q000473:pathology*; D009842:Oligopeptides; D061848:Optical Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005456:Fluorescent Dyes; D009842:Oligopeptides; C578342:cysteinyl-glutaminyl-arginyl-prolyl-prolyl-arginine
keywords: In vivo imaging; Ischemia and reperfusion injury; Myocardial cell death; Peptide probe