Linking smooth muscle cell plasticity and senescence in atherosclerosis: a role for RGS5
Description: Atherosclerosis is still a leading cause of death worldwide and has been mainly viewed as a lipid and leucocyte-driven process. Owing to lineage tracing and single cell studies we know now that smooth muscle cells (SMCs) are more abundant in the atherosclerotic plaque than originally thought and adopt alternative phenotypes whilst losing their contractile markers. Besides this phenotypic modulation, SMCs also undergo cellular senescence – a form of cellular ageing - during plaque progression. I have previously shown that SMC senescence promotes plaque destabilisation through inflammation but whether it also involves SMC phenotypic modulation remains unclear. Here, we aim to study the link between SMC senescence and plasticity, using 3D SMC spheroids, SMC lineage tracing, scRNA sequencing and senolytic drugs. Specifically, we aim to determine the role of RGS5 (Regulator of G-protein Signaling 5) in SMC phenotypic modulation and senescence in a mouse model of atherosclerosis and in human plaques, and test whether senolytic treatment can reverse SMC phenotypic modulation. Our secondary aim is to proof the added value of 3D imaging over classical 2D histology to study atherosclerosis in an unbiased and comprehensive manner. Overall, the use of 3D systems, both in cells as in mice, will give us a better understanding of the role of SMC plasticity and senescence and bring us closer to finding new therapeutic targets (e.g. RGS5 or its downstream targets) for atherosclerosis.
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: grant
Funder scheme: FWO research project (including WEAVE projects)
Start date: 2026-01-01
End date: 2029-12-31
Investigator: Mandy Grootaert
Institution: FWO
Funded outputs count: 0
Funder award ID: G039726N
OpenAlex ID: G5203149287