Vascular smooth muscle cell phenotypic switching and plaque stability: a role for CHI3L1.

Abstract

Vascular smooth muscle cells (VSMCs) play important and varied roles in the development and progression of atherosclerosis. VSMCs form the medial layer of arteries where they maintain vessel tone via their contractile function. Under normal conditions VSMCs remain quiescent, however in atherosclerotic cardiovascular disease these cells phenotypically switch to a ‘synthetic’ phenotype, characterised by downregulation of the contractile machinery, secretion of extracellular matrix (ECM) proteins, proliferation, and migration. VSMCs were traditionally thought to play a dichotomous role in atherosclerosis; VSMC proliferation drives lesion growth whereas ECM production results in fibrous cap formation in mature plaque, which stabilises lesions and prevents rupture1,2. Recently however, lineage tracing and single-cell RNA-sequencing profiling have revealed additional VSMCs plasticity in disease and shown that VSMCs generate cells resembling foam cells, macrophages, mesenchymal stem cells, and osteochondrogenic cells3–5. The importance of these phenotypes in vivo, and their functional impact on plaque growth and stability, is yet to be resolved.