Rheumatology Unit, University of Perugia, Perugia, Italy.
Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Arthritis Res Ther. 2022 Oct 24;24(1):236. doi: 10.1186/s13075-022-02930-7.
Endothelial dysfunction contributes to increased cardiovascular (CV) disease in rheumatoid arthritis (RA). Angiogenic T cells (Tang) are a key regulator of vascular function via their interaction with endothelial progenitor cells (EPCs). Methotrexate (MTX) has been associated to reduced CV disease risk, but its effects on endothelial homeostasis have been poorly explored. We investigated MTX effects on endothelial homeostasis in early, treatment-naïve RA patients.
Fifteen untreated, early RA patients and matched healthy controls (HC) were enrolled. RA patients with long-standing disease in remission or low disease activity treated with MTX for at least 6 months were selected as controls. Circulating CD28 and CD28 Tang cell, endothelial microparticle (EMP), EPC and soluble vascular cell adhesion molecule (sVCAM)-1 levels were measured.
Tang percentage was higher in early RA than in HCs and significantly increased after 3-month MTX treatment. Tang cells in RA were characterized by higher percentage of CD28 and lower CD28-positive cells than HCs. MTX restored a Tang cell phenotype similar to HCs. Altered sVCAM-1, EMP and EPC were restored to levels similar to HCs after a 3-month MTX. Biomarker levels after 3 months of MTX were not different to those of patients with long-standing treatment.
MTX has a positive effect on Tang, sVCAM-1, EPCs and EMPs in RA. Restoration of imbalance between CD28 + and CD28 Tang by MTX may be one of the mechanisms underlying its favourable effects on endothelial dysfunction. These effects seem to be long-lasting and independent from systemic inflammation reduction, suggesting a direct effect of MTX on the endothelium.
内皮功能障碍导致类风湿关节炎（RA）患者心血管（CV）疾病风险增加。血管生成 T 细胞（Tang）通过与内皮祖细胞（EPC）相互作用，是血管功能的关键调节因子。甲氨蝶呤（MTX）与降低 CV 疾病风险相关，但对内皮稳态的影响尚未得到充分探索。我们研究了 MTX 对早期未经治疗的 RA 患者内皮稳态的影响。
招募了 15 名未经治疗的早期 RA 患者和匹配的健康对照者（HC）。选择疾病缓解期或低疾病活动度且接受 MTX 治疗至少 6 个月的长期疾病 RA 患者作为对照。测量循环 CD28 和 CD28 Tang 细胞、内皮微颗粒（EMP）、EPC 和可溶性血管细胞黏附分子（sVCAM）-1 水平。
早期 RA 患者的 Tang 百分比高于 HC，且在 3 个月 MTX 治疗后显著增加。RA 患者的 Tang 细胞具有较高的 CD28 比例和较低的 CD28 阳性细胞比例。MTX 恢复了与 HC 相似的 Tang 细胞表型。改变的 sVCAM-1、EMP 和 EPC 在 3 个月 MTX 治疗后恢复到与 HC 相似的水平。3 个月 MTX 治疗后的生物标志物水平与长期治疗的患者无差异。
MTX 对 RA 患者的 Tang、sVCAM-1、EPC 和 EMP 具有积极影响。MTX 恢复 CD28+和 CD28 Tang 之间的失衡可能是其对内皮功能障碍有益影响的机制之一。这些影响似乎是持久的，与全身炎症减少无关，提示 MTX 对内皮有直接作用。
