Atherosclerosis is a serious cardiovascular disease that is characterised by the development of atheroma, which are lipid-laden plaques that build up within arterial walls due to chronic inflammatory processes. These lesions are fundamentally attributed to a complex cellular crosstalk between vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs) and central immune cells, such as macrophages (Mɸs), which promote vascular inflammation. The presence of VSMCs exerts both positive and negative effects during atheroma development, which can be attributed to their phenotypic plasticity. Understanding the interactions between these key cell types during the development of vascular inflammation and atheroma will enhance the scope for new therapeutic interventions. This study aims to determine the importance of VSMCs for shaping the extracellular cytokine/chemokine profile and transcriptional responses of VECs (human coronary artery endothelial cells; HCAECs) to activated lipopolysaccharide (LPS)-stimulated THP1 Mɸs, in a 3-cell model of human vascular inflammation. It is evident that within the presence of VSMCs, enhanced cytokine production was associated with up-regulation of genes associated with vascular inflammation t. Results demonstrate that the presence of VSMCs in co-culture experiments enhanced cytokine production (including CXCL1/GROα, IL-6, IL-8 and CCL2/MCP1) and inflammatory gene expression (including genes involved in JAK/STAT, Jun and NFκB signalling) in HCAECs co-cultured with LPS-stimulated THP1 Mɸs. Our results highlight the importance of VSMCs in immune/endothelial cell interplay and indicate that 3-cell, rather than 2-cell co-culture, may be more appropriate for the study of cellular crosstalk between immune and vascular compartments in response to inflammatory and atherogenic stimuli.

动脉粥样硬化是一种严重的心血管疾病，其特征是形成动脉粥样硬化斑块，动脉粥样硬化斑块是由于慢性炎症过程在动脉壁内形成的富含脂质的斑块。这些病变从根本上归因于血管平滑肌细胞（VSMC）、血管内皮细胞（VEC）和中枢免疫细胞（例如巨噬细胞（Mɸs））之间复杂的细胞串扰，从而促进血管炎症。 VSMC 的存在在动脉粥样硬化形成过程中发挥着积极和消极的作用，这可归因于其表型可塑性。了解这些关键细胞类型在血管炎症和动脉粥样硬化形成过程中之间的相互作用将扩大新治疗干预的范围。本研究旨在确定 VSMC 在人类 3 细胞模型中塑造细胞外细胞因子/趋化因子谱以及 VEC（人冠状动脉内皮细胞；HCAEC）对活化脂多糖 (LPS) 刺激的 THP1 Mɸs 的转录反应的重要性。血管炎症。很明显，在存在 VSMC 的情况下，细胞因子产生的增强与血管炎症相关基因的上调有关。结果表明，共培养实验中 VSMC 的存在增强了细胞因子的产生（包括 CXCL1/GROα、IL-6、IL-8 和 CCL2/MCP1）和炎症基因表达（包括参与 JAK/STAT、Jun 和 NFκB 信号传导的基因） ）在与 LPS 刺激的 THP1 Mɸs 共培养的 HCAEC 中。 我们的结果强调了 VSMC 在免疫/内皮细胞相互作用中的重要性，并表明 3 细胞而不是 2 细胞共培养可能更适合研究免疫和血管区室之间的细胞串扰，以响应炎症和动脉粥样硬化刺激。