Vascular smooth muscle cells enhance immune/vascular interplay in a 3-cell model of vascular inflammation
Wiejak, Jolanta and Murphy, Fiona A. and Maffia, Pasquale and Yarwood, Stephen J. (2023) Vascular smooth muscle cells enhance immune/vascular interplay in a 3-cell model of vascular inflammation. Scientific Reports, 13. 15889. ISSN 2045-2322 (https://doi.org/10.1038/s41598-023-43221-8)
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Abstract
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.
ORCID iDs
Wiejak, Jolanta, Murphy, Fiona A. ORCID: https://orcid.org/0000-0001-7925-0632, Maffia, Pasquale and Yarwood, Stephen J.;-
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Item type: Article ID code: 86834 Dates: DateEvent23 September 2023Published21 September 2023Accepted11 July 2023SubmittedSubjects: Medicine > Other systems of medicine Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 03 Oct 2023 11:22 Last modified: 16 Oct 2024 04:51 URI: https://strathprints.strath.ac.uk/id/eprint/86834