Background/Purpose: 1) To evaluate the association of inflammation, adipokines and endothelial dysfunction with the cardiovascular risk profile and the metabolic comorbidities associated with psoriatic arthritis (PsA). 2) To explore the effects of the inflammation on the glucose and lipid metabolism in the PsA context. 3) To analyze the effect of apremilast in the adipo/cytokine pattern, metabolic components and endothelial dysfunction in patients with PsA and metabolic syndrome (MetSyn).

Methods: Human study: 60 PsA patients and 30 age and gender-matched healthy donors (HD) were analyzed. An extensive clinical analysis was performed. Endothelial function was measured through post occlusive hyperemia using Laser-Doppler. Twelve PsA patients having metabolic syndrome were given apremilast 30 mg twice daily for 6 months. The levels of cytokines, endothelial dysfunction markers and adipokines were analyzed on serum and leukocytes by ELISA and RT-PCR, respectively. Treatment of adipocytes with serum from PsA patients: 3T3L1 adipocytes were treated with serum 10% of PsA patients and HD for 24h. The expression of genes and proteins involved in inflammation, lipid metabolism and insulin signalling was analysed.

Results:

MetSyn, obesity and insulin resistance (IR) were increased in PsA. PsA patients had impaired endothelial function. Levels of cytokines, adipokines and endothelial function markers were altered in PsA serum and leukocytes. Increased levels of HOMA-IR correlated with DAS28, clinical and serological inflammatory markers, and diverse adipokines. In addition, PsA serum induced inflammation and modified lipid and glucose metabolism in adipocytes, suggesting a link between the degree of systemic inflammation and the development of IR in these patients. After 6 months of treatment, Apremilast reduced BMI, insulin resistance, inflammation, and levels of ApoB. Adipokines profile was reversed and levels of Apo A increased. Endothelial dysfunction was significantly restored shown by an increase of the peak flow and hyperaemia area and decreased adhesion molecules in serum.

Conclusion:

1) PsA is associated with an increase of inflammatory cytokines and adipokines, alongside with an endothelial dysfunction. These alterations are related to the disease activity and the presence of metabolic comorbidities such as insulin resistance or obesity, contributing to the burden of cardiovascular disease risk. 2) The inflammatory components are directly involved in the development of IR in PsA. 3) Apremilast might reduce IR, inflammation and endothelial dysfunction, parameters strongly involved in cardiovascular disease.

Supported by the Minister of Health (ISCIII, PI17/01316, RIER RD16/0012/0015) cofinanced with FEDER funds.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interplay-among-inflammation-adipokines-and-endothelial-dysfunction-in-patients-with-psoriatic-arthritis-relationship-with-cardiovascular-and-metabolic-comorbidities-modulation-by-apremilast/