Department of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia.
Faculty of Mathematics, Natural Science and Information Technologies, University of Primorska, SI-6000 Koper, Slovenia.
Mediators Inflamm. 2018 Feb 13;2018:8237209. doi: 10.1155/2018/8237209. eCollection 2018.
RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients.
To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC).
HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically.
SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%.
We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.
与普通人群相比，类风湿关节炎（RA）患者的心血管疾病发病率更高。血清淀粉样蛋白 A（SAA）是一种急性期蛋白，在 RA 患者的血清中上调。
确定药物对 SAA 刺激的人冠状动脉内皮细胞（HCAEC）的影响。
将 HCAEC 用无菌小瓶中的药物（地塞米松、甲氨蝶呤、依那西普、和依那西普）预孵育 2 小时，溶于培养基（卡托普利）或 DMSO（依托考昔、罗格列酮、美洛昔康、氟伐他汀和双氯芬酸）。用人重组 apo-SAA 以终浓度 1000 nM 刺激 HCAEC 24 小时。通过 ELISA 测定 IL-6、IL-8、sVCAM-1 和 PAI-1 的水平。通过比色法测定活细胞数。
SAA 刺激的 HCAEC 释放的 IL-6、IL-8 和 sVCAM-1 水平被甲氨蝶呤、氟伐他汀和依托考昔显著降低。依那西普和依那西普平均降低 PAI-1 43%。罗格列酮显著抑制 sVCAM-1 58%。
我们观察到氟伐他汀对降低 SAA 激活的 HCAEC 细胞因子产生有明显影响。甲氨蝶呤对降低释放的 Il-6、IL-8 和 sVCAM-1 有很强的有益作用。非甾体抗炎药（NSAIDs）表现出有趣的双重性，美洛昔康与双氯芬酸和依托考昔的作用趋势相反。这代表了对与动脉粥样硬化相关的炎症驱动的 HCAEC 的特定反应性的独特见解。
