原花青素 B2 通过抑制人脐静脉内皮细胞核因子 kappa-B 通路减轻氧化型低密度脂蛋白诱导的细胞损伤、炎症、单核细胞趋化和氧化应激。

Procyanidin B2 alleviates oxidized low-density lipoprotein-induced cell injury, inflammation, monocyte chemotaxis, and oxidative stress by inhibiting the nuclear factor kappa-B pathway in human umbilical vein endothelial cells.

机构信息

Department of Cardiovascular, Henan University of Chinese Medicine, 63 Dongming Road, Henan province, Zhengzhou, 450063, China.

出版信息

BMC Cardiovasc Disord. 2024 Apr 29;24(1):231. doi: 10.1186/s12872-024-03858-3.

DOI:10.1186/s12872-024-03858-3

PMID:38679696

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11057093/

Abstract

BACKGROUND

Oxidized low-density lipoprotein (ox-LDL) can initiate and affect almost all atherosclerotic events including endothelial dysfunction. In this text, the role and underlying molecular basis of procyanidin B2 (PCB2) with potential anti-oxidant and anti-inflammatory activities in ox-LDL-induced HUVEC injury were examined.

METHODS

HUVECs were treated with ox-LDL in the presence or absence of PCB2. Cell viability and apoptotic rate were examined by CCK-8 assay and flow cytometry, respectively. The mRNA and protein levels of genes were tested by RT-qPCR and western blot assays, respectively. Potential downstream targets and pathways of apple procyanidin oligomers were examined by bioinformatics analysis for the GSE9647 dataset. The effect of PCB2 on THP-1 cell migration was examined by recruitment assay. The effect of PCB2 on oxidative stress was assessed by reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and mitochondrial membrane potential (MMP).

RESULTS

ox-LDL reduced cell viability, induced cell apoptosis, and facilitated the expression of oxidized low-density lipoprotein receptor 1 (LOX-1), C-C motif chemokine ligand 2 (MCP-1), vascular cell adhesion protein 1 (VCAM-1) in HUVECs. PCB2 alleviated ox-LDL-induced cell injury in HUVECs. Apple procyanidin oligomers triggered the differential expression of 592 genes in HUVECs (|logfold-change| > 0.58 and adjusted p-value < 0.05). These dysregulated genes might be implicated in apoptosis, endothelial cell proliferation, inflammation, and monocyte chemotaxis. PCB2 inhibited C-X-C motif chemokine ligand 1/8 (CXCL1/8) expression and THP-1 cell recruitment in ox-LDL-stimulated HUVECs. PCB2 inhibited ox-LDL-induced oxidative stress and nuclear factor kappa-B (NF-κB) activation in HUVECs.

CONCLUSION

PCB2 weakened ox-LDL-induced cell injury, inflammation, monocyte recruitment, and oxidative stress by inhibiting the NF-κB pathway in HUVECs.

摘要

背景

氧化型低密度脂蛋白（ox-LDL）可引发并影响几乎所有动脉粥样硬化事件，包括内皮功能障碍。在本文中，研究了具有潜在抗氧化和抗炎活性的原花青素 B2（PCB2）在 ox-LDL 诱导的 HUVEC 损伤中的作用及其潜在的分子机制。

方法

在存在或不存在 PCB2 的情况下，用 ox-LDL 处理 HUVEC。通过 CCK-8 测定和流式细胞术分别检测细胞活力和细胞凋亡率。通过 RT-qPCR 和 Western blot 测定分别检测基因的 mRNA 和蛋白水平。通过生物信息学分析 GSE9647 数据集检测苹果原花青素低聚物的潜在下游靶标和途径。通过募集测定法检测 PCB2 对 THP-1 细胞迁移的影响。通过测定活性氧（ROS）水平、丙二醛（MDA）含量和线粒体膜电位（MMP）评估 PCB2 对氧化应激的影响。

结果

ox-LDL 降低了 HUVEC 的细胞活力，诱导了细胞凋亡，并促进了氧化型低密度脂蛋白受体 1（LOX-1）、C-C 基序趋化因子配体 2（MCP-1）和血管细胞粘附蛋白 1（VCAM-1）的表达。PCB2 减轻了 ox-LDL 诱导的 HUVEC 细胞损伤。苹果原花青素低聚物在 HUVEC 中触发了 592 个基因的差异表达（|logfold-change|>0.58，调整后的 p 值<0.05）。这些失调的基因可能与细胞凋亡、内皮细胞增殖、炎症和单核细胞趋化有关。PCB2 抑制 ox-LDL 刺激的 HUVEC 中 C-X-C 基序趋化因子配体 1/8（CXCL1/8）的表达和 THP-1 细胞募集。PCB2 抑制 ox-LDL 诱导的氧化应激和核因子 kappa-B（NF-κB）在 HUVEC 中的激活。