Background/Purpose:

Psoriatic arthritis (PsA) and Psoriasis (PsO) are chronic inflammatory diseases associated with vascular inflammation and increased CVD risk. Few studies have examined vascular inflammatory differences between PsO and PsA and how these differences may impart a different CVD risk profile. We directly investigated the vascular endothelium of patients with PsA, PsO and compared to controls to better understand the inflammatory mechanism(s) that predispose psoriatic patients to CVD risk.

Methods:

Twenty patients with psoriatic disease (PD) (mean age 45 years, 55% male, 11.2 ± 19% body surface area (BSA) involvement) were first compared to 10 matched controls. Next, comparisons were made between PsO (n = 14, average age 50 years, 57% male, 11 ± 22% BSA) and active PsA (n = 6, average age 36 years, 50% male, 11 ± 10% BSA, average 2 – 3 tender/swollen joints per individual). To measure vascular endothelial health, venous endothelial cells were collected from the brachial vein using guidewires inserted through an angiocatheter and isolated with CD146-conjugated magnetic beads. Following collection, endothelial mRNA was isolated, converted to cDNA and inflammatory gene profiling performed by RT-qPCR with Taqman probes and primers. Transcripts were chosen based on in vitro gene arrays of human aortic endothelial cells co-stimulated with IL-17 and TNF-α.

Results:

PD patients compared to controls showed a trend towards higher levels of hs-CRP (2.4 ± 4 mg/dl vs. 0.8 ± 2 mg/dl, p = 0.08) with no overall difference noted between PsA and PsO patients (2.8 ± 2 mg/dl vs. 2.7 ± 4 mg/dl, p = 0.24). Transcriptomic profiling of venous endothelial cells comparing PD (PsO and PsA) to controls revealed upregulation of inflammatory cytokine- and chemokine- associated transcripts (lymphotoxin beta [4 – fold], CCL3 [11 – fold], CXCL10 [16 – fold], IL-8 [10 – fold] and IL-1β [4 – fold], P < 0.05 for all) and transcripts related to intracellular adhesion (ICAM1 [2.4 – fold] and inflammation COX-2 [3 – fold], P < 0.05). Increased expression of the chemokine fractalkine (CX3CL1 [2.8 – fold], p < 0.05) and lymphotoxin beta [2 – fold, p = 0.10] were found in patients with active PsA compared to PsO. No differences in CCL3, CXCL10, IL-8, IL-1B, ICAM1 and COX-2 where seen between PsA and PsO patients.

Conclusion:

Endothelial cell pro-inflammatory transcripts are upregulated in patients with active PD compared with controls. Levels of lymphotoxin beta and fractalkine, a chemokine present in inflamed arthritic synovial tissue, are greater in endothelial cells of patients with PsA than PsO. These findings may underlie increased CVD risk in patients with PD and highlight the inflammatory vascular differences between PsO and PsA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/vascular-endothelial-and-inflammatory-differences-in-psoriasis-and-psoriatic-arthritis-patients/