Authors
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, Chul Ahn, L Maximilian Buja, CS Raman, Sanjay S Shete, Dianna M Milewicz
Publication date
2007/12
Journal
Nature genetics
Volume
39
Issue
12
Pages
1488-1493
Publisher
Nature Publishing Group US
Description
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 α-actin (encoded by ACTA2) and the β-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 medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations …
Total citations
Scholar articles
DC Guo, H Pannu, V Tran-Fadulu, CL Papke, RK Yu… - Nature genetics, 2007