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Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patients With Rheumatoid Arthritis.

Ahmed A, Hollan I, Curran SA, Kitson SM, Riggio MP, Mikkelsen K, Almdahl SM, Aukrust P, McInnes IB, Goodyear CS - (2016)

Bottom Line: In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion.The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization.In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.

View Article: PubMed Central - PubMed

Affiliation: University of Glasgow, Glasgow, UK.

No MeSH data available.


Related in: MedlinePlus

IL‐33 and soluble ST2 (sST2) in late‐stage CVD patients with (n = 19) and those without (n = 20) RA. A and B, Immunohistologic evaluation and quantification of the percentage of vasa vasorum (VV) in the aortic adventitia (AA) that were positive for IL‐33 (A) and the percentage of IL‐33–positive endothelial cells (ECs) in each vasa vasorum (B). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Lines outside the boxes represent the 5th and 95th percentiles. C, Correlation between swollen joint counts and the percentage of IL‐33–positive ECs in each vasa vasorum. D, Serum levels of soluble ST2. Values are the mean ± SEM. ∗ = P < 0.05; ∗∗∗ = P = 0.002. See Figure 1 for other definitions.
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art39574-fig-0002: IL‐33 and soluble ST2 (sST2) in late‐stage CVD patients with (n = 19) and those without (n = 20) RA. A and B, Immunohistologic evaluation and quantification of the percentage of vasa vasorum (VV) in the aortic adventitia (AA) that were positive for IL‐33 (A) and the percentage of IL‐33–positive endothelial cells (ECs) in each vasa vasorum (B). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Lines outside the boxes represent the 5th and 95th percentiles. C, Correlation between swollen joint counts and the percentage of IL‐33–positive ECs in each vasa vasorum. D, Serum levels of soluble ST2. Values are the mean ± SEM. ∗ = P < 0.05; ∗∗∗ = P = 0.002. See Figure 1 for other definitions.

Mentions: IL‐33 was detected in the majority of aortic adventitia biopsy specimens from both RA patients (88%) and non‐RA patients (72%) but was restricted to the nucleus of vasa vasorum ECs (additional information is available upon request from the corresponding author). The proportion of vasa vasora expressing IL‐33 (IL‐33+ vasa vasorum) was higher in RA patients compared with non‐RA patients (mean ± SEM 20.4 ± 15.8% versus 8.6 ± 9.5%; P = 0.02) (Figure 2A). The proportion of EC nuclei positive for IL‐33 within each vasa vasorum (IL‐33+ ECs) was also substantially greater in RA patients compared with non‐RA patients (mean ± SEM 58.7 ± 34.1% versus 32.9 ± 28.5%; P = 0.02) (Figure 2B). In the internal thoracic artery, the proportion of IL‐33+ vasa vasorum was similar in RA patients (89%) and non‐RA patients (79%), but RA patients had a higher proportion of IL‐33+ ECs (30.6 ± 26.3% versus 13.1 ± 12.5%; P = 0.04). The proportions of IL‐33+ ECs and IL‐33+ vasa vasorum in aortic adventitia did not correlate with any traditional CV risk factors (additional information is available upon request from the corresponding author). In RA patients, the proportion of IL‐33+ ECs in aortic adventitia was significantly correlated with NYHA functional class (r = 0.618, P = 0.018) but not with other markers of CVD severity. Furthermore, the proportion of IL‐33+ ECs in the aortic adventitia of RA patients was also significantly correlated with the tender joint count (r = 0.582, P = 0.023) (data not shown) and the swollen joint count (r = 0.619, P = 0.014) (Figure 2C).


Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patients With Rheumatoid Arthritis.

Ahmed A, Hollan I, Curran SA, Kitson SM, Riggio MP, Mikkelsen K, Almdahl SM, Aukrust P, McInnes IB, Goodyear CS - (2016)

IL‐33 and soluble ST2 (sST2) in late‐stage CVD patients with (n = 19) and those without (n = 20) RA. A and B, Immunohistologic evaluation and quantification of the percentage of vasa vasorum (VV) in the aortic adventitia (AA) that were positive for IL‐33 (A) and the percentage of IL‐33–positive endothelial cells (ECs) in each vasa vasorum (B). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Lines outside the boxes represent the 5th and 95th percentiles. C, Correlation between swollen joint counts and the percentage of IL‐33–positive ECs in each vasa vasorum. D, Serum levels of soluble ST2. Values are the mean ± SEM. ∗ = P < 0.05; ∗∗∗ = P = 0.002. See Figure 1 for other definitions.
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art39574-fig-0002: IL‐33 and soluble ST2 (sST2) in late‐stage CVD patients with (n = 19) and those without (n = 20) RA. A and B, Immunohistologic evaluation and quantification of the percentage of vasa vasorum (VV) in the aortic adventitia (AA) that were positive for IL‐33 (A) and the percentage of IL‐33–positive endothelial cells (ECs) in each vasa vasorum (B). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Lines outside the boxes represent the 5th and 95th percentiles. C, Correlation between swollen joint counts and the percentage of IL‐33–positive ECs in each vasa vasorum. D, Serum levels of soluble ST2. Values are the mean ± SEM. ∗ = P < 0.05; ∗∗∗ = P = 0.002. See Figure 1 for other definitions.
Mentions: IL‐33 was detected in the majority of aortic adventitia biopsy specimens from both RA patients (88%) and non‐RA patients (72%) but was restricted to the nucleus of vasa vasorum ECs (additional information is available upon request from the corresponding author). The proportion of vasa vasora expressing IL‐33 (IL‐33+ vasa vasorum) was higher in RA patients compared with non‐RA patients (mean ± SEM 20.4 ± 15.8% versus 8.6 ± 9.5%; P = 0.02) (Figure 2A). The proportion of EC nuclei positive for IL‐33 within each vasa vasorum (IL‐33+ ECs) was also substantially greater in RA patients compared with non‐RA patients (mean ± SEM 58.7 ± 34.1% versus 32.9 ± 28.5%; P = 0.02) (Figure 2B). In the internal thoracic artery, the proportion of IL‐33+ vasa vasorum was similar in RA patients (89%) and non‐RA patients (79%), but RA patients had a higher proportion of IL‐33+ ECs (30.6 ± 26.3% versus 13.1 ± 12.5%; P = 0.04). The proportions of IL‐33+ ECs and IL‐33+ vasa vasorum in aortic adventitia did not correlate with any traditional CV risk factors (additional information is available upon request from the corresponding author). In RA patients, the proportion of IL‐33+ ECs in aortic adventitia was significantly correlated with NYHA functional class (r = 0.618, P = 0.018) but not with other markers of CVD severity. Furthermore, the proportion of IL‐33+ ECs in the aortic adventitia of RA patients was also significantly correlated with the tender joint count (r = 0.582, P = 0.023) (data not shown) and the swollen joint count (r = 0.619, P = 0.014) (Figure 2C).

Bottom Line: In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion.The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization.In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.

View Article: PubMed Central - PubMed

Affiliation: University of Glasgow, Glasgow, UK.

No MeSH data available.


Related in: MedlinePlus