Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo
T Quillard1, K Croce, F A Jaffer
1Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Imaging macrophage protease activity in vivo offers new ways to track cardiovascular diseases like atherosclerosis. This approach aids in evaluating disease progression and treatment effectiveness, potentially improving patient care.
Area of Science:
- Cardiovascular biology
- Medical imaging
- Protease biology
Background:
- Macrophages are central to cardiovascular diseases (CVD), including atherosclerosis.
- Proteolytic enzymes, particularly matrix metalloproteinases (MMPs) and cysteinyl cathepsins, are key macrophage effectors in CVD.
- In vivo imaging of macrophage protease activity could enhance disease and therapy evaluation.
Purpose of the Study:
- To explore the potential of intravital imaging for detecting protease activity in macrophages.
- To assess the utility of novel imaging agents for evaluating atherosclerosis, aortic aneurysms, and cardiac allograft rejection.
Main Methods:
- Development and exploration of activatable fluorescent probes.
- Utilization of radiolabeled inhibitors for imaging.
- Investigation of nanoparticles for protease activity detection.
Main Results:
- Various imaging agents and technologies are under development for detecting protease activity.
- Some agents are nearing clinical application, while others require further refinement.
- Intravital imaging of macrophages and protease activity shows promise for in vivo studies.
Conclusions:
- In vivo imaging of macrophage protease activity is a valuable tool for understanding CVD pathophysiology.
- This imaging modality can aid in evaluating the efficacy of therapeutic interventions.
- The advancement of these imaging techniques holds potential for improving clinical care in cardiovascular medicine.
Abstract:
Macrophages contribute pivotally to cardiovascular diseases (CVD), notably to atherosclerosis. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Proteolytic enzymes serve as key effectors of many macrophage contributions to CVD. Therefore, intravital imaging of protease activity could aid evaluation of the progress and outcome of atherosclerosis, aortic aneurysm formation, or rejection of cardiac allografts. Among the large families of proteases, matrix metalloproteinases (MMPs) and cysteinyl cathepsins have garnered the most interest because of their participation in extracellular matrix remodelling. These considerations have spurred the development of dedicated imaging agents for protease activity detection. Activatable fluorescent probes, radiolabelled inhibitors, and nanoparticles are currently under exploration for this purpose. While some agents and technologies may soon see clinical use, others will require further refinement. Imaging of macrophages and protease activity should provide an important adjunct to understanding pathophysiology in vivo, evaluating the effects of interventions, and ultimately aiding clinical care.
