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Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease. Vasc Med 2012 Apr;17(2):101-7

Date

04/13/2012

Pubmed ID

22496207

Pubmed Central ID

PMC3632403

DOI

10.1177/1358863X12440117

Abstract

Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor kappa B (NFlB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover study design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6-week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60 ± 10, 22% female) completed all the visits, with a high rate of study withdrawal due to gastrointestinal side effects. In a subset of 10 participants, we compared the effects of 4 days of sulfasalazine treatment (n = 5) to no treatment (n = 5) on NFκB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFlB activity; however, long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk.

Author List

Tabit CE, Holbrook M, Shenouda SM, Dohadwala MM, Widlansky ME, Frame AA, Kim BH, Duess MA, Kluge MA, Levit A, Keaney JF Jr, Vita JA, Hamburg NM

Author

Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aged
Analysis of Variance
Anti-Inflammatory Agents, Non-Steroidal
Biomarkers
Boston
Brachial Artery
Coronary Artery Disease
Cross-Over Studies
Double-Blind Method
Endothelium, Vascular
Female
Fingers
Humans
Inflammation Mediators
Leukocytes
Male
Manometry
Middle Aged
NF-kappa B
Predictive Value of Tests
Sulfasalazine
Time Factors
Treatment Outcome
Ultrasonography, Doppler
Vasodilation
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d