Role of vascular smooth muscle cells (VSMCs) in cardiovascular disease

Accumulation of vascular smooth muscle cells (VSMCs) is a hallmark of cardiovascular diseases such as atherosclerosis, which cause heart attack and stroke. In healthy vessels, VSMC contraction regulate blood flow and blood pressure but loose their contractile function and undergo extensive transformation upon vasuclar insult. This process results in the generation of a wide spectrum of phenotypically changed cells within atherosclerotic lesions, which are predicted to impact differently on disease progression. Using clonal lineage tracing in mouse models of atherosclerosis, we demonstrated that disease-associated cell accumulation result from extensive proliferation of a small subset of VSMC that can generate the full range of distinct cells. By combining lineage tracing with single cell RNA sequencing (sc-RNAseq) in mouse models, we have identified signatures of VSMC-derived cells subpopulations. Interestingly, cells displaying mesenchymal stem cell character are rare in healthy vessels and their numbers increase in disease models. The aim of this project is to understand how specific VSMC-derived cell populations in human disease arise, using a combination of genomics and functional assays, in order to allow efficient cell targeting in atherosclerotic lesions.