1. Cellular mechanisms of oligoclonal VSMC expansion in cardiovascular disease
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Jorgensen, Helle, Worssam, Matthew, Lambert, Jordi, Oc, Sebnem, Taylor, James, Taylor, Annabel, Dobnikar, Lina, Chappell, Joel, Harman, Jennifer L, Figg, Nichola L, Finigan, Alison, Foote, Kirsty, Uryga, Anna, Bennett, Martin R, Spivakov, Mikhail, Jorgensen, Helle [0000-0002-7909-2977], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Myocytes, Smooth Muscle ,Lineage tracing ,Atherosclerosis ,Muscle, Smooth, Vascular ,Clonal dynamics ,Phenotype ,Cardiovascular Diseases ,Vascular smooth muscle cells ,Animals ,Humans ,Spinocerebellar Ataxias ,Single-cell transcriptomics ,Cells, Cultured ,Cell Proliferation - Abstract
Aims Quiescent, differentiated adult vascular smooth muscle cells (VSMCs) can be induced to proliferate and switch phenotype. Such plasticity underlies blood vessel homeostasis and contributes to vascular disease development. Oligoclonal VSMC contribution is a hallmark of end-stage vascular disease. Here we aim to understand cellular mechanisms underpinning generation of this VSMC oligoclonality. Methods and Results We investigate the dynamics of VSMC clone formation using confocal microscopy and single cell transcriptomics in VSMC-lineage-traced animal models. We find that activation of medial VSMC proliferation occurs at low frequency after vascular injury and that only a subset of expanding clones migrate, which together drives formation of oligoclonal neointimal lesions. VSMC contribution in small atherosclerotic lesions is typically from one or two clones, similar to observations in mature lesions. Low frequency (