Mediator Med23 deficiency in smooth muscle cells prevents neointima formation after arterial injury

Vascular smooth muscle cells (VSMCs) that line the arteries and veins, are able to increase their proliferation rate greatly following vessel wall injury and in atherogenesis. Changes in VSMC proliferation rate and differentiation state have been proposed as required procedures of injury repair. The regulation of the balance between proliferation and differentiation is of key importance in vascular biology. Our previous works have shown that Mediator MED23 subunit restricts smooth muscle cell lineage development and promotes growth related gene expression 1 . Recently, we investigated the roles of Med23 in VSMC proliferation and differentiation as well as injury-induced neointima formation by generating and examining the smooth muscle specific Med23 -knockout ( Med23 sm−/ − ) mice. Our results showed that Med23 regulates the balance of VSMC growth and differentiation in mouse aorta. The Med23 sm − / − mice showed enlarged lumen and impaired contractility of aorta. RNA profiling of the aorta samples revealed that gene expression programs switching between proliferation and differentiation upon the presence or absence of Med23. More importantly, we found that Med23 deficiency prevented neointima formation after vascular injuries, through repressing VSMC proliferation. Collectively, our data demonstrate that Med23 has positive effects on VSMC plasticity and plays a novel pathological role in vascular injury induced neointima formation through promoting the proliferation and growth of VSMCs, thus providing a novel mechanism understanding the VSMC plasticity and related vascular diseases.