Abstract 11890: S100A8/A9 is Increased in Psoriasis Serum, Relates to Vascular Diseases and Activates Human Endothelial Cells

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Heather Teague ◽  
Qimin Ng ◽  
Monica Purmalek ◽  
Balaji Natarajan ◽  
Taufiq Salahuddin ◽  
...  

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.

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Eun Jin Park ◽  
Jae Seon Eo ◽  
Won-Young Jang ◽  
Dong Oh Kang ◽  
Cheol Ung Choi ◽  
...  

Backgrounds: Chronic mental stress is a major risk factor of coronary artery disease, but there is a lack of direct mechanistic evidence between brain amygdala activity, a neural stress center, versus plaque vulnerability in acute coronary syndrome. In this study, we aimed to evaluate whether brain amygdala activity in AMI patients assessed by 18 F-FDG PET/CT could be associated with vascular inflammation in carotid beds and high-risk coronary plaque features evaluated by OCT. Methods and Results: In retrospective analysis, the patients who underwent 18 F-FDG PET/CT and CAG at Korea University Guro Hospital (Seoul, Korea). Among 1802 patients underwent 18 F-FDG PET/CT from October 1 2009 to 31 December 31 2015, 230 patients received CAG. After excluding 36 patients who had active cancer or brain disease, 198 were stratified according to degree of coronary severity by syntax score [none (n=159); mild to moderate (n=26); severe (n=13)]. Brain amygdalar activity on PET was quantified as target-to-background ratio (TBR) of standardized uptake value (amygdalar SUV max /temporal SUV mean ). The amygdalar TBR was significantly higher in patients with severe coronary disease rather than those without coronary stenosis or mild to moderate stenosis assessed by syntax score (P=0.03). Intriguingly, among 13 patients with severe CAD, the amygdalar TBR significantly increased in the 6 patients presented as AMI compared to non-MI patients (P=0.03). In following prospective study, we performed 18 F-FDG PET/CT in AMI patients underwent percutaneous coronary intervention within index admission period, and in patients with chronic stable angina (CSA) as control. The plaque morphology in non-culprit segment of infarct-related artery (IRA) was estimated by OCT in AMI patients. Brain amygdalar TBR was significantly higher in AMI patients compared to CSA patients (p<0.05). In AMI patients, amygdalar activity was significantly associated with vascular inflammation quantified as carotid TBR (p<0.05). The increased amygdalar activity was associated with high-risk plaque characteristics of non-culprit segments of IRA. Conclusions: The amygdalar activity assessed by 18 F-FDG PET/CT was significantly higher in patients with AMI than CSA. This amygdalar activity was related to vulnerable plaque characteristics of IRA. Our results suggest that brain emotional activity in ACS could contribute to plaque instability in pan-vascular beds.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Ahmed Tawakol ◽  
Gregory R Wojtkiewicz ◽  
Peter K Henke ◽  
Ralph Weissleder ◽  
...  

Objective: While venous thrombosis (VT)-induced inflammation facilitates thrombus resolution, inflammation causes vein wall scarring (VWS). Recently, statins have shown to improve VT resolution and reduce VT inflammatory components. In this study, we hypothesized that early VT inflammation detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) could predict subsequent late stage VWS, and would be attenuated by statin therapy. Methods: Stasis VT was induced in 8-12 week old male C57BL/6 mice (n=31) in either the right jugular vein (n=13) or inferior vena cava (IVC,n=18). Animals in the IVC VT cohort were randomized to statin (n=8) or control (n=10) treatment. Statin, rosuvastatin (5mg/kg), was administered by oral gavage, daily starting 24 hours prior to VT induction; control mice received saline. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG inflammation signals (standard uptake value=SUV) were measured in the thrombosed vein and compared to the sham-operated venous segments or treatment control. On day 14, mice were sacrificed and VT tissue was resected. Picrosirius red staining allowed measurement of collagen and vein wall thickness in VT sections. Results: FDG-PET/CT at day 2 revealed increased inflammation signal activity in jugular VT (SUV 1.43 ± 0.3 VT vs. 0.81 ± 0.3 contralateral vein, p<0.0001). Statin-treated mice showed a trend of decreased inflammation signal at day 2 in the IVC VT models (SUV 1.02 ± 0.1 statin VT vs. 1.42 ± 0.2 control VT, p=0.07). Day 14 histological analysis revealed significantly reduced vein wall injury in statin-treated animals (thickness, 32±9.4 μm statin; vs. 56.2±14.7 μm control, p=0.02). Day 2 FDG-PET inflammation in VT correlated positively with the magnitude of day 14 VWS (jugular VT, Spearman r=0.62, p=0.02; IVC VT r=0.74, p<0.001, respectively). Conclusions: Quantitative FDG-PET/CT imaging demonstrates that early in vivo VT inflammation predicts subsequent VWS, a driver of post-thrombotic syndrome (PTS). The overall findings strengthen: (i) the link between inflammation and PTS; (ii) the translational potential of FDG-PET inflammation to predict VWS and PTS; and (iii) the concept that statins and other anti-inflammatory therapies could reduce VWS and PTS.


2013 ◽  
Vol 61 (10) ◽  
pp. E1056
Author(s):  
Nehal N. Mehta ◽  
Nikhil H. Sheth ◽  
Joshua Baker ◽  
Alexis Ogdie ◽  
Anna Raper ◽  
...  

2018 ◽  
Vol 71 (11) ◽  
pp. A1481
Author(s):  
Agastya Belur ◽  
Youssef Elnabawi ◽  
Amit Dey ◽  
Aparna Sajja ◽  
Aditya Goyal ◽  
...  

2016 ◽  
Vol 32 (10) ◽  
pp. S152-S153
Author(s):  
V. Corrales-Medina ◽  
C. Habibi ◽  
R. deKemp ◽  
P. Macpherson ◽  
C. Kelly ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Skye Hsin-Hsien Yeh ◽  
Ming Hsien Lin ◽  
I. I. Leo Garcia Flores ◽  
Uday Mukhopadhyay ◽  
Danial Young ◽  
...  

Combining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types and stages of cancer in vitro and in vivo. Detection of changes in HDAC activity/expression may provide important prognostic and predictive information and influence treatment decision-making. Use of [18F] FAHA, a HDAC IIa-specific radionuclide, for molecular imaging may enable longitudinal, noninvasive assessment of HDAC activity/expression in metastatic cancer. We evaluated the synergistic anticancer effects of cisplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in xenograft models of nonsmall cell lung cancer (NSCLC) using [18F] FAHA and [18F] FDG PET/CT imaging. Cisplatin alone significantly increased [18F] FAHA accumulation and reduced [18F] FDG accumulation in H441 and PC14 xenografts; coadministration of cisplatin and SAHA resulted in the opposite effects. Immunochemical staining for acetyl-histone H3 confirmed the PET/CT imaging findings. Moreover, SAHA had a more significant effect on the acetylome in PC14 (EGFR exon 19 deletion mutation) xenografts than H441 (wild-type EGFR and KRAS codon 12 mutant) xenografts. In conclusion, [18F] FAHA enables quantitative visualization of HDAC activity/expression in vivo, thus, may represent a clinically useful, noninvasive tool for the management of patients who may benefit from synergistic anticancer therapy.


2017 ◽  
Vol 16 ◽  
pp. 153601211769744 ◽  
Author(s):  
Maria I. Menendez ◽  
Bianca Hettlich ◽  
Lai Wei ◽  
Michael V. Knopp

Sign in / Sign up

Export Citation Format

Share Document