Actin alpha 2 (ACTA2) (ACTA2)

Actin alpha 2 (ACTA2), also known as alpha-smooth muscle actin (a-SMA), is a protein that in humans is encoded by the ACTA2 gene and is a major component of the contractile apparatus in vascular smooth muscle cells [1, 2]. It plays a pivotal role in maintaining vascular tone and blood pressure, and its expression is tightly regulated under normal physiological conditions [2]. In the context of disease, ACTA2 is a definitive marker for the transition of fibroblasts into myofibroblasts, which are the primary cells responsible for the excessive deposition of extracellular matrix in fibrotic disorders of the liver, lung, and kidney [3]. Mutations in the ACTA2 gene are a known cause of thoracic aortic aneurysms and dissections (TAAD), highlighting its importance in vascular structural integrity [4]. Therapeutic targeting of ACTA2 mRNA using RNA interference (RNAi) or antisense oligonucleotides (ASOs) is an emerging strategy to treat chronic fibrosis by reducing the population of activated myofibroblasts [5]. While direct small-molecule inhibitors are not standard, the modulation of ACTA2 expression is a key endpoint in the development of various anti-fibrotic and oncology drugs [3, 5].

Other names

Alpha-smooth muscle actina-SMAACTSAMYSS1Aortic smooth muscle actin

Inhibition of protein translation through RNA interference or RNase H-mediated degradation of the mRNA transcript [5].