UnTEThering (Smooth Muscle) Cell Plasticity

Cellular plasticity has become the subject of intense research, with perhaps the greatest example provided by the recent Nobel Prize winners Drs Yamananka and Gurdon and the demonstration that terminally differentiated fibroblasts can be coaxed into assuming an embryonic stem cell-like fate. Emerging evidence suggests that plasticity inherent in cells may be hijacked in the progression of disease and cancer. However, the mechanisms by which cells acquire and regulate this plasticity remain incompletely understood. It is appreciated that broad programs must be unleashed during these switches, and, therefore, control at the epigenetic level in regulating these processes has garnered significant interest. In this issue of Circulation , Liu et al1 provide evidence implicating the epigenetic factor termed ten-eleven translocation-2 (TET2) in control of vascular smooth muscle cell (VSMC) plasticity and development of vascular disease.Article see p 2047Under homeostatic conditions, the principal function of the VSMC is regulation of vascular tone through the expression of unique contractile proteins, agonist receptors, and ion channels.2 The differentiated contractile phenotype is characterized by the expression of cytoskeletal marker proteins, including smooth muscle actin (ACTA2 [for actin, α2, smooth muscle, aorta]) and smooth muscle-myosin heavy chain (MYH11 [for myosin, heavy chain 11, smooth muscle]). However, unlike other terminally differentiated muscle cell types (skeletal or cardiac), VSMCs exhibit a high degree of phenotype plasticity. In response to injury or damage, VSMCs assume a dedifferentiated synthetic phenotype characterized by a high proliferative index, loss of contractile properties and proteins, and production of extracellular matrix products. This phenotype plasticity, first described by Chamley-Campbell et al3 >3 decades ago, is observed both in vitro …