Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Sci Rep. 2021 Feb 17;11(1):3972. doi: 10.1038/s41598-021-83252-7.
Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1β, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (T) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.
最近的试验表明,系统性抗炎治疗可减少冠心病 (CAD) 患者的心血管事件。我们最近证明,植物乳杆菌 299v (Lp299v) 补充可改善稳定 CAD 男性的血管内皮功能。这种有利影响是否部分归因于抗炎作用尚不清楚。为了验证这一假设,我们将这些受试者在补充 Lp299v 前后获得的血浆暴露于健康供体的 PBMC 中,并测量 PBMC 转录组的差异,进行基因本体分析,并将 Lp299v 诱导的转录组变化与血管功能变化进行比较。每日饮酒者 (DAU) (n = 4) 对 Lp299v 的反应明显不同,因此从主要分析中分离出来。非 DAU 组 (n = 15) 显示出更好的肱动脉血流介导的扩张 (FMD) 和循环中 IL-8、IL-12 和瘦素水平降低。997 个基因发生了显著变化。I.I.com 降低 (1.01 ± 0.74 与 0.22 ± 0.51;P < 0.0001),表明具有很强的抗炎作用。通路分析显示 IL-1β、干扰素刺激途径和 Toll 样受体信号转导下调,调节性 T 细胞 (T) 活性增加。GBP1、JAK2 和 TRAIL 表达的降低与 FMD 的改善相关。在稳定 CAD 的非 DAU 男性中,Lp299v 补充后的血浆在人类 PBMC 中诱导抗炎转录组变化,可能有益于 CAD 患者。未来的研究应该阐明负责这些影响的循环代谢物的变化。