1st Department of Neurology, Faculty of Medicine, Comenius University, 813 69 Bratislava, Slovakia.
Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia.
Int J Mol Sci. 2023 Jul 6;24(13):11162. doi: 10.3390/ijms241311162.
Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma.
MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated.
The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, = 0.001), the use of GLP-1a therapy (beta = 0.560, = 0.003), and small LDL (beta = 0.339, = 0.043) were the only significant variables in the model that predicted the follow-up RHI.
Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.
流行病学研究表明，多发性硬化症（MS）患者的血管风险增加。越来越多的证据表明 GLP-1 激动剂（GLP-1a）在预防血管并发症和减缓神经退行性变方面具有有益作用。我们的目的是探讨 GLP-1a 治疗 12 个月后 MS 患者内皮功能的变化。我们还探讨了脂蛋白亚组分的作用和血浆抗氧化能力。
MS 患者纳入前瞻性、单中心研究。13 例患者给予 GLP-1a（度拉糖肽）治疗。对照组由 12 名受试者组成。内皮功能通过外周动脉张力测定法确定，并表示为再灌注充血指数（RHI）。用 Trolox 等效抗氧化能力（TEAC）评估血浆的总抗氧化能力。评估脂蛋白亚组分的水平。
GLP-1a 组治疗 12 个月后 RHI 无显著变化（2.1±0.6 与 2.1±0.7；=0.807）。然而，TEAC 显著增加（4.1±1.4 与 5.2±0.5mmol/L，=0.010）。相反，对照组受试者的 RHI 显著恶化（2.1±0.5 与 1.8±0.6；=0.030），TEAC 无显著变化。除极低密度脂蛋白（VLDL）显著下降（30.8±10.2 与 22.6±8.3mg/dL，=0.043）外，对照组其他变量无显著变化。VLDL 水平（β=-0.637，=0.001）、GLP-1a 治疗（β=0.560，=0.003）和小 LDL（β=0.339，=0.043）是预测随访 RHI 的唯一显著变量。
我们的结果表明，在高 MS 活动的 MS 患者中应用额外的 GLP-1a 治疗可能具有抗动脉粥样硬化和抗氧化作用，从而可能前瞻性地降低其血管风险。然而，脂蛋白谱也可能在 MS 患者的动脉粥样硬化风险中发挥重要作用。
