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Published on: August 28, 2018
Cysteine proteases in atherosclerosis
Tommy Weiss-Sadan1, Israel Gotsman2, Galia Blum1
1The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Insights
Cysteine cathepsins play a key role in atherosclerosis development by affecting lipid metabolism, inflammation, and apoptosis. Understanding these proteases offers new avenues for cardiovascular disease diagnostics and therapeutics.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Molecular Medicine
Background:
- Atherosclerosis, a precursor to cardiovascular diseases like myocardial infarction and stroke, involves lipid and inflammatory cell retention in the vascular endothelium.
- Vascular lesions initially harmless can progress due to chronic inflammation and remodeling, leading to arterial wall damage and thrombotic events.
Purpose of the Study:
- To elucidate the function of cysteine cathepsins in cellular processes dysregulated in atherosclerosis.
- To explore the contribution of cathepsins to arterial remodeling and atherogenesis.
- To review advancements in protease molecular imaging for cardiovascular event prediction.
Main Methods:
- Review of human tissue evidence and preclinical animal models.
- Analysis of the role of cysteine cathepsins in lipid metabolism, inflammation, and apoptosis.
- Exploration of protease molecular imaging techniques.
Main Results:
- Cysteine cathepsins are integral to the development and progression of vascular lesions in atherosclerosis.
- Dysfunctional cellular processes including lipid metabolism, inflammation, and apoptosis are influenced by cathepsins.
- Protease molecular imaging presents potential as a diagnostic marker for cardiovascular events.
Conclusions:
- Targeting cysteine cathepsins presents therapeutic opportunities for atherosclerosis.
- Advanced molecular imaging of proteases may serve as a surrogate marker for identifying future cardiovascular events.
Abstract:
Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen. Evidence from human tissues and preclinical animal models has clearly established the role of cathepsin cysteine proteases in the development and progression of vascular lesions. Hence, understanding the function of cathepsins in atherosclerosis is important for developing novel therapeutic strategies and advanced point of care diagnostics. In this review we will describe the roles of cysteine cathepsins in different cellular process that become dysfunctional in atherosclerosis, such as lipid metabolism, inflammation and apoptosis, and how they contribute to arterial remodeling and atherogenesis. Finally, we will explore new horizons in protease molecular imaging, which may potentially become a surrogate marker to identify future cardiovascular events.
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