Circ Cardiovasc Imaging. 2013 May 1;6(3):441-7 doi: 10.1161/circimaging.112.000074. 2013 Mar 30.

Fluorescence tomography of rapamycin-induced autophagy and cardioprotection in vivo

Chen HH, Mekkaoui C, Cho H, Ngoy S, Marinelli B, Waterman P, Nahrendorf M, Liao R, Josephson L, Sosnovik DE.

Abstract

BACKGROUND: Autophagy is a biological process during which cells digest organelles in their cytoplasm and recycle the constituents. The impact of autophagy in the heart, however, remains unclear in part because of the inability to noninvasively image this process in living animals. METHODS AND RESULTS: Here, we report the use of fluorescence molecular tomography and a cathepsin-activatable fluorochrome to image autophagy in the heart in vivo after ischemia/reperfusion and rapamycin (RAP) therapy. We show that cathepsin-B activity in the lysosome is upregulated by RAP and that this allows the expanded lysosomal compartment in autophagy to be imaged in vivo with fluorescence molecular tomography. We further demonstrate that the delivery of diagnostic nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The upregulation of autophagy by RAP was associated with a 23% reduction (P

PMID: 23537953