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  • Lyons, OliverSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)

Human venous valve disease caused by mutations in FOXC2 and GJC2

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-07-19
  • Rockefeller University Press,2017
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-359802
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-359802URI
  • https://doi.org/10.1084/jem.20160875DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events. Genetic deletion of Gjc2, Gja4, or Gja1 also disrupted early VV Prox1(hi) endothelial organization at postnatal day 0, and this likely underlies the VV defects seen in patients with GJC2 mutations. Knockout of Gja4 or Gjc2 resulted in reduced proliferation of Prox1(hi) valve-forming cells. At later stages of blood flow, Foxc2 and calcineurin-Nfat signaling are each required for growth of the valve leaflets, whereas Foxc2 is not required for VV maintenance.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Saha, PrakashSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Seet, ChristopherSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Kuchta, AdamGuys & St Thomas NHS Fdn Trust, Dept Ultrason Angiol, London, England (author)
  • Arnold, AndrewGuys & St Thomas NHS Fdn Trust, Dept Ultrason Angiol, London, England (author)
  • Grover, StevenHarvard Med Sch, Boston, MA USA;Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA (author)
  • Rashbrook, VictoriaSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Sabine, AmelieUniv Lausanne, Div Expt Pathol, Ctr Hosp Univ Vaudois, Epalinges, Switzerland;Ludwig Inst Canc Res, Dept Fundamental Oncol, Zurich, Switzerland (author)
  • Vizcay-Barrena, GemaKings Coll London, Ctr Ultrastruct Imaging, London, England (author)
  • Patel, AshSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Ludwinski, FrancescaSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Padayachee, SoundrieGuys & St Thomas NHS Fdn Trust, Dept Ultrason Angiol, London, England (author)
  • Kume, TsutomuNorthwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Evanston, IL USA (author)
  • Kwak, Brenda R.Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland (author)
  • Brice, GlenSt George Hosp, South West Thames Reg Genet Serv, London, England (author)
  • Mansour, SaharSt George Hosp, South West Thames Reg Genet Serv, London, England (author)
  • Ostergaard, PiaSt George Hosp, Cardiovasc & Cell Sci Inst, London, England (author)
  • Mortimer, PeterSt George Hosp, Cardiovasc & Cell Sci Inst, London, England (author)
  • Jeffery, SteveSt George Hosp, Cardiovasc & Cell Sci Inst, London, England (author)
  • Brown, NigelSt George Hosp, Inst Med & Biomed Educ, London, England (author)
  • Mäkinen, TaijaUppsala universitet,Vaskulärbiologi(Swepub:uu)taima352 (author)
  • Petrova, Tatiana V.Univ Lausanne, Div Expt Pathol, Ctr Hosp Univ Vaudois, Epalinges, Switzerland;Ludwig Inst Canc Res, Dept Fundamental Oncol, Zurich, Switzerland (author)
  • Modarai, BijanSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • Smith, AlbertoSt Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, England (author)
  • St Thomas Hosp, Acad Dept Vasc Surg, Cardiovasc Div, BHF Ctr Res Excellence,Kings Coll London, London, EnglandGuys & St Thomas NHS Fdn Trust, Dept Ultrason Angiol, London, England (creator_code:org_t)

Related titles

  • In:Journal of Experimental Medicine: Rockefeller University Press214:8, s. 2437-24520022-10071540-9538

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