Molecular and Cellular Control of Macrophage/Endothelial Cell Cross-talk in a 3-cell Model of Atheroma

Jun07Wed

Molecular and Cellular Control of Macrophage/Endothelial Cell Cross-talk in a 3-cell Model of Atheroma

Wed, 07/06/2023 - 13:30 to 14:30

Location:

Speaker: 
Stephen Yarwood
Affiliation: 
Heriot Watt
Synopsis: 

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). 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 atheroma will enhance the scope for new therapeutic interventions. This study aims to determine the importance of VSMC for shaping the extracellular cytokine/chemokine profile and transcriptional responses of VECs (human coronary artery endothelial cells; HCAECs) to activated LPS-stimulated THP1 Mɸs, in a 3-cell model of human atheroma. It is evident that within the presence of VSMCs, enhanced cytokine production was associated with up-regulation of genes associated with inflammation and subsequent atheroma development. Results demonstrate that the presence of VSMCs in co-culture experiments enhanced cytokine production and inflammatory gene expression in HCAECs co-cultured with LPS-stimulated THP1 Mɸs. Our results highlight the importance of VSMCs in immune/endothelial cell cross-talk 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.

Institute: