TY - JOUR
T1 - In vivo imaging of myocardial cell death using a peptide probe and assessment of long-term heart function
AU - Acharya, Bodhraj
AU - Wang, Kai
AU - Kim, In San
AU - Kang, Woongchol
AU - Moon, Chanil
AU - Lee, Byung Heon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2008-0061891 ), WCU (World Class University) program through the NRF funded by the Ministry of Education, Science and Technology ( R33-10054 ), and Converging Research Center program through the Ministry of Science, ICT and Future Planning, Korea ( 2013K000338 ).
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - In vivo imaging
KW - Ischemia and reperfusion injury
KW - Myocardial cell death
KW - Peptide probe
UR - http://www.scopus.com/inward/record.url?scp=84884606232&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2013.08.294
DO - 10.1016/j.jconrel.2013.08.294
M3 - Article
C2 - 24021357
AN - SCOPUS:84884606232
SN - 0168-3659
VL - 172
SP - 367
EP - 373
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -