ArticlePloS one2016
Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies.Journal of cellular and molecular medicine · 2024Review
- Article
- Overview of multifunctional cysteinyl cathepsins in atherosclerosis-based cardiovascular disease: from insights into molecular functions to clinical implications.Cell & bioscience · 2023Review
- The Protective Role of TREM2 in the Heterogenous Population of Macrophages during Post-Myocardial Infarction Inflammation.International journal of molecular sciences · 2023Review
- Activity-based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity.Angewandte Chemie (International ed. in English) · 2022Article
- Methyltetrazine as a small live-cell compatible bioorthogonal handle for imaging enzyme activitiesRSC chemical biology · 2022Article
- TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target.Molecular neurodegeneration · 2022Review
- Activated molecular probes for enzyme recognition and detection.Theranostics · 2022Review
- Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Currently Available Strategies for Target Identification of Bioactive Natural Products.Frontiers in chemistry · 2021Review
- Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples.Frontiers in chemistry · 2021Review
- Macrophage subsets in atherosclerosis as defined by single-cell technologies.The Journal of pathology · 2020Review
- High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils.Biological procedures online · 2020Article
- Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety.Molecular imaging and biology · 2019Review
- Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer.Pharmaceuticals (Basel, Switzerland) · 2019Review
- A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases.Theranostics · 2019Article
- Neutrophil Elastase Activity Imaging: Recent Approaches in the Design and Applications of Activity-Based Probes and Substrate-Based Probes.Contrast media & molecular imaging · 2019Review
- Advanced Activity-Based Protein Profiling Application Strategies for Drug Development.Frontiers in pharmacology · 2018Review
- Chemical Modulation ofACS central science · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCardiovascular disease is the leading cause of death worldwide, mainly due to an increasing prevalence of atherosclerosis characterized by inflammatory plaques. Plaques with high levels of macrophage infiltration are considered "vulnerable" while those that do not have significant inflammation are considered stable; cathepsin protease activity is highly elevated in macrophages of vulnerable plaques and contributes to plaque instability. Establishing novel tools for non-invasive molecular imaging of macrophages in plaques could aid in preclinical studies and evaluation of therapeutics. Furthermore, compounds that reduce the macrophage content within plaques should ultimately impact care for this disease.
methodsWe have applied quenched fluorescent cathepsin activity-based probes (ABPs) to a murine atherosclerosis model and evaluated their use for in vivo imaging using fluorescent molecular tomography (FMT), as well as ex vivo fluorescence imaging and fluorescent microscopy. Additionally, freshly dissected human carotid plaques were treated with our potent cathepsin inhibitor and macrophage apoptosis was evaluated by fluorescent microscopy.
resultsWe demonstrate that our ABPs accurately detect murine atherosclerotic plaques non-invasively, identifying cathepsin activity within plaque macrophages. In addition, our cathepsin inhibitor selectively induced cell apoptosis of 55%±10% of the macrophage within excised human atherosclerotic plaques.
conclusionsCathepsin ABPs present a rapid diagnostic tool for macrophage detection in atherosclerotic plaque. Our inhibitor confirms cathepsin-targeting as a promising approach to treat atherosclerotic plaque inflammation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.