A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases
Autor: | David Maimoun, Ihab Abd-Elrahman, Emmanuelle Merquiol, Yael Ben-Nun, Galia Blum, Israel Gotsman, Tommy Weiss-Sadan |
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Rok vydání: | 2019 |
Předmět: |
Proteases
medicine.medical_treatment activity-based probes Medicine (miscellaneous) Fluorescent Antibody Technique Photodynamic therapy Disease 010402 general chemistry 01 natural sciences Mass Spectrometry 030218 nuclear medicine & medical imaging 03 medical and health sciences Mice 0302 clinical medicine Immune system In vivo Medicine Animals Pharmacology Toxicology and Pharmaceutics (miscellaneous) Stroke Cathepsin business.industry Macrophages medicine.disease Atherosclerosis Cysteine protease Cathepsins Mice Mutant Strains 0104 chemical sciences Photochemotherapy Receptors LDL photodynamic therapy Cardiovascular Diseases Cancer research Female Collagen business Research Paper |
Zdroj: | Theranostics |
ISSN: | 1838-7640 |
Popis: | 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. |
Databáze: | OpenAIRE |
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