Abstract 11890: S100A8/A9 is Increased in Psoriasis Serum, Relates to Vascular Diseases and Activates Human Endothelial Cells
Introduction: Psoriasis is a chronic inflammatory disorder of the skin affecting 2-4% of the population and is associated with an increased risk of cardiovascular events, specifically myocardial infarction.
Methods: In a large, ongoing prospective cohort study of psoriasis and cardiovascular diseases (NCT01778569), we studied a consecutive sample (n=100) and aimed to investigate the potential role that S100A8/A9 may have in linking psoriasis to CV disease measured by FDG PET CT and coronary CTA. Furthermore, we conducted in vitro experiments on human aortic endothelial cells (ECs) to examine whether treatement with S100A9 activates these cells. We hypothesized that S100A8/A9 would relate to psoriasis severity, relate to in vivo vascular inflammation by FDG PET CT, non-calcified burden of coronary disease by CCTA and increase endothelial cell activation.
Results: We observed that the S100A8/A9 heterodimer was elevated in serum (mean psoriasis: 2019 ± 100.1; non-psoriasis: 1634 ± 160.7; p = 0.02), correlating both with psoriasis severity score (adjusted β = 0.53, p = 0.02) and overall aortic vascular inflammation measured by FDG PET CT (adjusted β = 0.48, p = 0.02) beyond the Framingham Risk Score. Additionally, we found that S100A8/A9 was associated with direct coronary atherosclerosis measured by coronary CTA demonstrating an increase in total (β = 0.16, p = 0.04) and non-calcified plaque burden (β = 0.23, p = 0.003) but not dense calcified burden. When EC's were treated with S100A9, ICAM1, E-Selectin and VCAM1 gene expression levels increased 10-fold (p = 0.001), 86-fold (P = 0.007) and 20-fold (p = 0.0002) respectively compared to the untreated human aortic endothelial cells.
Conclusions: S100A8/A9 related to psoriasis severity, in vivo vascular inflammation, non-calcified plaque in the coronary arteries and EC activation. These findings suggest this protein may play a role in linking psoriasis to CVD and a role in early atherosclerotic plaque formation. Ongoing studies aim to elucidate the source of S100A8/A9 in the blood and to characterize the signaling pathway utilized by S100A8/A9 to understand whether this pathway is broadly applicable to vascular diseases associated with chronic inflammation.
Author Disclosures: H. Teague: None. Q. Ng: None. M. Purmalek: None. B. Natarajan: None. T. Salahuddin: None. E. Stansky: None. T. Aridi: None. M.P. Playford: None. M.J. Kaplan: None. N.N. Mehta: None.
- © 2015 by American Heart Association, Inc.