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A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases

Despite the common use of lipid-lowering medications, cardiovascular diseases continue to be a significant health concern. Atherosclerosis, one of the most frequent causes of cardiovascular morbidity, involves extensive inflammatory activity and remodeling of the vascular endothelium. This relentles...

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Autores principales: Weiss-Sadan, Tommy, Ben-Nun, Yael, Maimoun, David, Merquiol, Emmanuelle, Abd-Elrahman, Ihab, Gotsman, Israel, Blum, Galia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735363/
https://www.ncbi.nlm.nih.gov/pubmed/31534515
http://dx.doi.org/10.7150/thno.34402
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author Weiss-Sadan, Tommy
Ben-Nun, Yael
Maimoun, David
Merquiol, Emmanuelle
Abd-Elrahman, Ihab
Gotsman, Israel
Blum, Galia
author_facet Weiss-Sadan, Tommy
Ben-Nun, Yael
Maimoun, David
Merquiol, Emmanuelle
Abd-Elrahman, Ihab
Gotsman, Israel
Blum, Galia
author_sort Weiss-Sadan, Tommy
collection PubMed
description Despite the common use of lipid-lowering medications, cardiovascular diseases continue to be a significant health concern. Atherosclerosis, one of the most frequent causes of cardiovascular morbidity, involves extensive inflammatory activity and remodeling of the vascular endothelium. This relentless inflammatory condition can ultimately give rise to clinical manifestations, such as ischemic heart disease or stroke. Accumulating evidence over the past decades implicates cysteine protease cathepsins in cardiovascular disorders. In particular, Cathepsins B, L, and S are over-expressed during vascular inflammation, and their activity is associated with impaired clinical outcomes. Here we took advantage of these molecular events to introduce a non-invasive detection and treatment approach to modulate vascular inflammation using a Photosensitizing quenched Activity-Based Probed (PS-qABP) that targets these proteases. Methods: We tested the application of this approach in LDL receptor-deficient mice and used non-invasive imaging and heart cross-section staining to assess the theranostic efficacy of this probe. Moreover, we used fresh human endarterectomy tissues to analyze cathepsin signals on gel, and verified cathepsin identity by mass spectrometry. Results: We showed that our PS-qABP can rapidly accumulate in areas of inflammatory atheromas in vivo, and application of light therapy profoundly reduced lesional immune cell content without affecting smooth muscle cell and collagen contents. Lastly, using human tissue samples we provided proof-of-concept for future clinical applications of this technology. Conclusions: Photodynamic therapy guided by cysteine cathepsin activity is an effective approach to reduce vascular inflammation and attenuate atherosclerosis progression. This approach could potentially be applied in clinical settings.
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spelling pubmed-67353632019-09-18 A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases Weiss-Sadan, Tommy Ben-Nun, Yael Maimoun, David Merquiol, Emmanuelle Abd-Elrahman, Ihab Gotsman, Israel Blum, Galia Theranostics Research Paper Despite the common use of lipid-lowering medications, cardiovascular diseases continue to be a significant health concern. Atherosclerosis, one of the most frequent causes of cardiovascular morbidity, involves extensive inflammatory activity and remodeling of the vascular endothelium. This relentless inflammatory condition can ultimately give rise to clinical manifestations, such as ischemic heart disease or stroke. Accumulating evidence over the past decades implicates cysteine protease cathepsins in cardiovascular disorders. In particular, Cathepsins B, L, and S are over-expressed during vascular inflammation, and their activity is associated with impaired clinical outcomes. Here we took advantage of these molecular events to introduce a non-invasive detection and treatment approach to modulate vascular inflammation using a Photosensitizing quenched Activity-Based Probed (PS-qABP) that targets these proteases. Methods: We tested the application of this approach in LDL receptor-deficient mice and used non-invasive imaging and heart cross-section staining to assess the theranostic efficacy of this probe. Moreover, we used fresh human endarterectomy tissues to analyze cathepsin signals on gel, and verified cathepsin identity by mass spectrometry. Results: We showed that our PS-qABP can rapidly accumulate in areas of inflammatory atheromas in vivo, and application of light therapy profoundly reduced lesional immune cell content without affecting smooth muscle cell and collagen contents. Lastly, using human tissue samples we provided proof-of-concept for future clinical applications of this technology. Conclusions: Photodynamic therapy guided by cysteine cathepsin activity is an effective approach to reduce vascular inflammation and attenuate atherosclerosis progression. This approach could potentially be applied in clinical settings. Ivyspring International Publisher 2019-08-12 /pmc/articles/PMC6735363/ /pubmed/31534515 http://dx.doi.org/10.7150/thno.34402 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Weiss-Sadan, Tommy
Ben-Nun, Yael
Maimoun, David
Merquiol, Emmanuelle
Abd-Elrahman, Ihab
Gotsman, Israel
Blum, Galia
A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title_full A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title_fullStr A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title_full_unstemmed A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title_short A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
title_sort theranostic cathepsin activity-based probe for noninvasive intervention in cardiovascular diseases
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735363/
https://www.ncbi.nlm.nih.gov/pubmed/31534515
http://dx.doi.org/10.7150/thno.34402
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