Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease.
Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease.
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DOI：
10.1177/1358863x12440117
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Hamburg NM
中科院分区：
文献类型：
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作者：
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
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 κB (NFκB), 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 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 four days of sulfasalazine treatment (n=5) to no treatment (n=5) on NFkB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFκB 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 NFκB 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 NFκB inhibition to reduce cardiovascular risk.
