Journal article

Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections

Dong-Chuan Guo, Hariyadarshi Pannu, Van Tran-Fadulu, Christina L Papke, Robert K Yu, Nili Avidan, Scott Bourgeois, Anthony L Estrera, Hazim J Safi, Elizabeth Sparks, David Amor, Lesley Ades, Vivienne McConnell, Colin E Willoughby, Dianne Abuelo, Marcia Willing, Richard A Lewis, Dong H Kim, Steve Scherer, Poyee P Tung Show all

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2007

Abstract

The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic ..

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