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

Nature Genetics, ISSN: 1061-4036, Vol: 39, Issue: 12, Page: 1488-1493
2007
  • 729
    Citations
  • 0
    Usage
  • 307
    Captures
  • 4
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    729
    • Citation Indexes
      719
    • Policy Citations
      7
      • Policy Citation
        7
    • Clinical Citations
      3
      • PubMed Guidelines
        3
  • Captures
    307
  • Mentions
    4
    • References
      4
      • Wikipedia
        4

Article 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 causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta. © 2007 Nature Publishing Group.

Bibliographic Details

Guo, Dong-Chuan; Pannu, Hariyadarshi; Tran-Fadulu, Van; Papke, Christina L; Yu, Robert K; Avidan, Nili; Bourgeois, Scott; Estrera, Anthony L; Safi, Hazim J; Sparks, Elizabeth; Amor, David; Ades, Lesley; McConnell, Vivienne; Willoughby, Colin E; Abuelo, Dianne; Willing, Marcia; Lewis, Richard A; Kim, Dong H; Scherer, Steve; Tung, Poyee P; Ahn, Chul; Buja, L Maximilian; Raman, C S; Shete, Sanjay S; Milewicz, Dianna M

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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