Annabel Taylor

Supervisor: Dr Helle Jørgensen

Title: Disease priming in the aorta: mechanisms underlying differential response of atherosclerosis-prone and resistant vascular smooth muscle cell populations

Abstract: Vascular smooth muscle cells (VSMCs) show inherent plasticity, allowing them to phenotypically switch and become “synthetic” in order to repair the blood vessels they encapsulate. Under inflammatory conditions, this process contributes to atherosclerotic plaque development, with VSMCs demonstrated to produce multiple plaque-resident cell types.

We have demonstrated that only a small fraction of VSMCs participate in disease-associated proliferation, but it is unclear if this is a defined cellular subset within a heterogeneous VSMC population. To address this question and functionally characterise the associated mechanisms, we will first use VSMC-specific lineage tracing to compare phenotypic switching in VSMCs from two aortic regions with different disease susceptibility. Next, candidate genes showing differential expression between healthy VSMC in single cell expression profiling will be assessed for functional implication in VSMC plasticity using siRNA knockdown. Finally, testing of selected genes for effects on remodelling following vascular injury will verify their importance for VSMC proliferation in disease.