Phenotypic transition (or transdifferentiation) of vascular smooth muscle cells (VSMC) plays a pivotal role in atherosclerosis. This phenomenom allows these cells to migrate from the media to the intima of arteries where they contribute to atherosclerotic lesions development and secrete numerous pro-inflammatory mediators. Migration and inflammation are also features of cancer cells. Molecules that regulate these properties, especially in carcinoma cells, have been identified. It is the case of the transcription factor Slug (or Snail2) which, by allowing epithelial to mesenchymal transition of pre-cancerous epithelial cells, participates in their transformation into invasive carcinoma cells. Our results show for the first time that Slug is well detectable in differentiated and transdifferentiated VSMC. Silencing of the gene encoding Slug inhibits by about 50% to 60% interleukine-1β (IL-1β) induction of pro-migratory and pro-inflammatory genes such as MMP (matrix metalloproteinases) 9 and 13, type IIa secretory phospholipase A2, inducible nitric oxide synthase and CCL3 (CC-motif ligand 3) and CXL2 (CXC motif ligand 2) chemokines in VSMC. These results indicate that Slug could be involved in IL-1β-induced VSMC phenotypic transition especially as we show that IL-1β up-regulates Slug protein level in VSMC. This effect is independent from a genic effect. Slug is described to be a very unstable protein in non cancerous epithelial cells and its stabilization by growth factors during malignant transformation usually involves glycogen synthase kinase-3β inhibition. However we demonstrate that IL-1β doesn’t inhibit this enzyme in VSMC which excludes its involvment in IL-1β-induced Slug protein level in VSMC. All together, our results highlight the potential role of Slug in atherogenesis, a role which would come to be added to the well established one that it plays in carcinoma cells invasion.

The author hereby declares no conflict of interest