Related Experiment Video
Updated: Mar 16, 2026
Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion
Ihab Abd-Elrahman1, Hisanori Kosuge2, Tommy Wises Sadan1
1The Institute of Drug Research, The School of Pharmacy, The Faculty of Medicine, The Hebrew University, Jerusalem, 9112001, Israel.
Insights
Novel activity-based probes (ABPs) detect macrophages in atherosclerotic plaques. A cathepsin inhibitor reduced macrophage content in human plaques, showing promise for treating cardiovascular disease.
Area of Science:
- Biomedical imaging
- Molecular diagnostics
- Cardiovascular research
Background:
- Cardiovascular disease is a leading global cause of death, driven by atherosclerosis.
- Inflammatory plaques, particularly those with high macrophage infiltration, are considered vulnerable.
- Cathepsin protease activity in macrophages elevates in vulnerable plaques, contributing to instability.
Purpose of the Study:
- To develop non-invasive molecular imaging tools for detecting macrophages in atherosclerotic plaques.
- To evaluate cathepsin activity-based probes (ABPs) for in vivo and ex vivo imaging.
- To assess the therapeutic potential of cathepsin inhibitors in reducing plaque inflammation.
Main Methods:
- Applied quenched fluorescent cathepsin ABPs to a murine atherosclerosis model.
- Utilized fluorescent molecular tomography (FMT) for in vivo imaging.
- Performed ex vivo fluorescence imaging, fluorescent microscopy, and evaluated macrophage apoptosis in human carotid plaques treated with a cathepsin inhibitor.
Main Results:
- Demonstrated accurate non-invasive detection of murine atherosclerotic plaques using ABPs.
- Identified cathepsin activity specifically within plaque macrophages.
- Showed that the cathepsin inhibitor selectively induced apoptosis in 55%±10% of macrophages in human atherosclerotic plaques.
Conclusions:
- Cathepsin ABPs serve as a rapid diagnostic tool for macrophage detection in atherosclerotic plaques.
- Cathepsin-targeting represents a promising therapeutic strategy for atherosclerotic plaque inflammation.
Background And Purpose:
Cardiovascular 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.
Methods:
We 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.
Results:
We 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.
Conclusions:
Cathepsin 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.
More Related Videos
09:43In vivo Near Infrared Fluorescence NIRF Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis
Published on: August 4, 2011
08:13Microwave-driven Synthesis of Iron Oxide Nanoparticles for Fast Detection of Atherosclerosis
Published on: March 22, 2016