Macrophage specific delivery of photosensitizer and light activation reduce inflammation and burden of atherosclerotic plaque via activation of autophagy and efferocytosis of apoptotic cells

Author(s):  
Joon Woo Song ◽  
Jae Won Ahn ◽  
Min Woo Lee ◽  
Hyun Jung Kim ◽  
Dong Oh Kang ◽  
...  
Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joon Woo Song ◽  
Min Woo Lee ◽  
Hyun Jung Kim ◽  
Jiseon Min ◽  
Un Gyo Kang ◽  
...  

Introduction: Autophagy plays a protective role in atherosclerosis and can promote efferocytosis of apoptotic cells. Photoactivation is a promising tool for treating cardiovascular disease, and induces autophagy in macrophages-derived foam cells, however, regulation of autophagy and efferocytosis by photoactivation in atherosclerotic plaque remains unknown. Objective: The present study aims to investigate whether macrophage targeted light activation induces autophagy and enhances efferocytosis in inflamed plaques Methods and Results: Targeted photoactivatable agent showed specific binding affinity and phototoxicity to scavenger receptor-expressing macrophages. Confocal microscopy analysis over time after irradiation demonstrated the induction of apoptosis and autophagy flux in macrophage-derived foam cells. The theranostic agent localized to macrophage scavenger receptors within atherosclerotic plaques, and intravital fluorescence microscopy imaged plaque inflammation and was used to monitor photobleaching after irradiation. Serial in vivo imaging analysis demonstrated that macrophage-specific photoactivation reduced plaque burden and inflammation after 1 week (Figure A). Mechanistically, targeted light activation induced autophagy within atheroma as early as 1 day (Figure B), and increased phagocytic receptor Mer tyrosine kinase (MerTK) expression. Targeted photoactivation had 2-fold-increase in macrophage-associated apoptotic bodies at one week after laser irradiation, indicating enhanced efferocytosis (Figure C). Conclusions: As a sensitive multifunctional therapeutic and imaging strategy, macrophage targeted photoactivation with autophagy induction could confer a promising theranostic strategy for the high-risk plaques.


2000 ◽  
Vol 110 (3) ◽  
pp. 322-329 ◽  
Author(s):  
M. Miginiac-Maslow ◽  
K. Johansson ◽  
E. Ruelland ◽  
E. Issakidis-Bourguet ◽  
I. Schepens ◽  
...  

2000 ◽  
Vol 110 (3) ◽  
pp. 295-295
Author(s):  
Louise Anderson ◽  
Per Gardestrom

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
ME Czerwińska ◽  
A Filipek ◽  
AK Kiss ◽  
JA Polański ◽  
RM Proczka ◽  
...  

2020 ◽  
Author(s):  
RQ Ramos ◽  
RR Moraes ◽  
GC Lopes

Clinical Relevance The use of multipeak LED light-curing guarantees efficiency on light activation of Ivocerin-containing light-cured resin cement.


2010 ◽  
Vol 14 (1) ◽  
pp. 88-93 ◽  
Author(s):  
Radim Farana ◽  
Lačezar Ličev ◽  
Jaromír Škuta ◽  
Štěpán Sojka ◽  
Michal Bar ◽  
...  

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