Inhibition of Nuclear Factor‐KappaB Improves Nitric Oxide‐Dependent Dilation in the Cutaneous Microvasculature of Psoriatic Adults
Authors: Alba Billie K. , Greaney Jody L. , Ferguson Sara B. , Alexander Lacy M. 
Published: June 2021

Psoriasis is a chronic autoimmune disease and is associated with an increased risk of cardiovascular mortality. Systemic inflammation characteristic of psoriasis contributes to the development of cardiovascular disease (CVD) by inducing peripheral vascular dysfunction. Inflammatory signals involved in the pathogenesis of psoriasis activate the universal transcription factor, nuclear factor κB (NFκB). NFκB activation has been strongly linked to vascular dysfunction through multiple mechanisms that reduce nitric oxide (NO) bioavailability. However, the role of NFκB activation in contributing to microvascular endothelial dysfunction has not been examined in psoriatic adults. We tested the hypothesis that systemic inhibition of NFκB (high‐dose oral salsalate) would improve NO‐mediated endothelium‐dependent vasodilation in psoriatic adults. Eight adults (3M, 5F; 35 ± 6 yr) with moderate plaque psoriasis (11% lesional body surface area) and eight healthy age‐ and sex‐matched non‐psoriatic adults (3M, 5F; 37 ± 6 yr) ingested salsalate (3000 mg/d) or placebo for 4 days in a randomized, cross‐over design. On the fourth day of the intervention, microvascular endothelial function was assessed utilizing a physiological eNOS‐dependent stimulus combined with intradermal microdialysis in a non‐lesional skin site on the forearm. Red cell flux (laser Doppler flowmetry) was measured during local skin heating (42°C), until an established plateau had been reached. Then NO‐dependent vasodilation was directly quantified through perfusion of the nonspecific NO synthase inhibitor NG‐nitro‐l‐arginine methyl ester (15 mM). Cutaneous vascular conductance (CVC = red cell flux/mean arterial pressure) was calculated and normalized to a percentage of maximum (28 mM sodium nitroprusside, 43°C). Plasma salicylate concentrations were similarly elevated following salsalate treatment in psoriatic and healthy adults (psoriasis: 24.0 ± 8.5 vs healthy: 22.2 ± 7.9 mg/dL; p=0.51). In psoriatic adults, C‐reactive protein (CRP) concentrations were clinically elevated during placebo (3.4 ± 1.2 mg/L) but not during salsalate treatment (1.5 ± 0.5 mg/L). NO‐dependent vasodilation was reduced in psoriatic adults compared to healthy adults during placebo (psoriasis: 20.9 ± 5.1 vs healthy: 40.1 ± 7.3 %CVCmax; p = 0.051) but not during salsalate treatment (psoriasis: 32.2 ± 3.7 vs healthy: 31.4 ± 6.2 %CVCmax; p = 0.86). These preliminary data suggest that inhibition of NFκB improves NO‐mediated endothelium‐dependent vasodilation in psoriatic adults. Treatment strategies for psoriasis that target inflammatory signaling pathways, specifically NFκB, may secondarily improve vascular function and reduce psoriasis‐associated CVD risk.

Support or Funding Information

Supported by AHA 16PRE31060000 and NIH R01HL093238; author views not official US Army or DOD policy

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.