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S100A8 and S100A9 in cardiovascular biology and disease
Michelle M Averill1, Claus Kerkhoff, Karin E Bornfeldt
1Department of Pathology, Diabetes and Obesity Center of Excellence, 815 Mercer St, University of Washington, Seattle, WA 98109-8055, USA.
Insights
Damage-associated molecular pattern molecules S100A8 and S100A9 are implicated in cardiovascular disease. Understanding their roles may lead to new therapeutic strategies for cardiovascular conditions.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- S100A8 and S100A9 (S100A8/A9) are damage-associated molecular pattern molecules with significant roles in inflammation.
- These proteins are expressed by myeloid and vascular cells during inflammatory and autoimmune conditions.
- S100A8/A9 exhibit both intracellular and extracellular functions, modulating inflammatory pathways via Toll-like receptor 4 and the receptor for advanced glycation end products.
Purpose of the Study:
- To investigate the roles of S100A8 and S100A9 in cardiovascular science.
- To elucidate the mechanisms by which S100A8/A9 mediate their biological effects in vascular cells.
- To explore the potential of S100A8/A9 as therapeutic targets for cardiovascular diseases.
Main Methods:
- The study reviews existing literature on S100A8 and S100A9 in cardiovascular contexts.
- Analysis of protein expression patterns in inflammatory and autoimmune states.
- Examination of functional roles in preclinical models (e.g., Apoe(-)(/)(-) mice).
Main Results:
- Increased plasma levels of S100A8/A9 are predictive of cardiovascular events in humans.
- Deletion of S100A8/A9 provides partial protection against atherosclerosis in Apoe(-)(/)(-) mice.
- S100A8/A9 possess both pro-inflammatory and anti-inflammatory/immune regulatory actions.
Conclusions:
- S100A8 and S100A9 are key players in cardiovascular inflammation and disease pathogenesis.
- Further understanding of S100A8/A9 in vascular cells can inform novel therapeutic strategies.
- Targeting S100A8/A9 may offer new avenues for preventing, treating, and predicting cardiovascular diseases.
Abstract:
There is recent and widespread interest in the damage-associated molecular pattern molecules S100A8 and S100A9 in cardiovascular science. These proteins have a number of interesting features and functions. For example, S100A8 and S100A9 (S100A8/A9) have both intracellular and extracellular actions, they are abundantly expressed in inflammatory and autoimmune states, primarily by myeloid cells but also by other vascular cells, and they modulate inflammatory processes, in part through Toll-like receptor 4 and the receptor for advanced glycation end products. S100A8/A9 also have anti-inflammatory and immune regulatory actions. Furthermore, increased plasma levels of S100A8/A9 predict cardiovascular events in humans, and deletion of these proteins partly protects Apoe(-)(/)(-) mice from atherosclerosis. Understanding the roles of S100A8 and S100A9 in vascular cell types and the mechanisms whereby these proteins mediate their biological effects may offer new therapeutic strategies to prevent, treat, and predict cardiovascular diseases.
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