Smooth Muscle Differentiation Control Comes Full Circle
The Circular Noncoding RNA, circActa2, Functions as a miRNA Sponge to Fine-Tune α-SMA Expression
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Atherosclerosis is a chronic inflammatory disease that progresses to complex, unstable arterial lesions.1 Restenosis is an acute inflammatory vascular disease and a major limitation of percutaneous angioplasty procedures.2 Both are characterized by dedifferentiation of vascular smooth muscle cells (SMCs) resulting in neointimal hyperplasia and vessel occlusion. Differentiated SMCs are highly specialized cells whose primary role is to maintain vessel homeostasis, vessel tone, blood pressure, and blood flow distribution.3 This function is driven through expression of SMC-specific contractile and contractile-related proteins, including SMMHC (smooth muscle myosin heavy chain/Myh11), α-SMA (α-smooth muscle actin/Acta2), SM22α (Tagln1), and calponin (Cnn1), among others. Unlike terminally differentiated cardiac and skeletal muscle, SMCs retain a significant degree of phenotypic plasticity, exhibiting the ability to undergo extensive changes in phenotype in response to specific stimuli (ie, dedifferentiated SMC). SMC dedifferentiation is associated with a transition to a highly proliferative, inflammatory phenotype characterized by downregulation of SMC-specific genes and increased production of multiple inflammatory and matrix-associated mediators. Thus, SMCs are major contributors to vascular disease progression, and defining molecular mechanisms regulating SMC phenotypic transitions is critical to define novel therapeutics for the treatment of vascular disease.
Article, see p 628
Regulation of SMC differentiation is complex, involving multiple signaling pathways and transcriptional regulators. Most SMC-specific genes are under transcriptional control by the transcription factor, serum response factor (SRF), and its cardiac and SMC-specific cofactor, myocardin, the SRF–myocardin axis.3–5 SRF binds the serum response element or CArG box, in which one or more are present within promoter and intronic regions of SMC-specific genes.3,4 In contrast, myocardin does not directly bind DNA, but transactivates SMC-specific genes through its interaction with SRF.5 Although the SRF–myocardin axis is central to transcriptional regulation of SMC genes, additional factors and mechanisms have been …