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A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

Author

Listed:
  • Eleni Tzima

    (The Scripps Research Institute
    University of North Carolina at Chapel Hill)

  • Mohamed Irani-Tehrani

    (The Scripps Research Institute)

  • William B. Kiosses

    (The Scripps Research Institute)

  • Elizabetta Dejana

    (University of Milan)

  • David A. Schultz

    (University of California at San Diego)

  • Britta Engelhardt

    (University of Bern)

  • Gaoyuan Cao

    (University of Pennsylvania Medical Center)

  • Horace DeLisser

    (University of Pennsylvania Medical Center)

  • Martin Alexander Schwartz

    (The Scripps Research Institute
    University of Virginia)

Abstract

Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis1, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression2,3,4. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-κB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.

Suggested Citation

  • Eleni Tzima & Mohamed Irani-Tehrani & William B. Kiosses & Elizabetta Dejana & David A. Schultz & Britta Engelhardt & Gaoyuan Cao & Horace DeLisser & Martin Alexander Schwartz, 2005. "A mechanosensory complex that mediates the endothelial cell response to fluid shear stress," Nature, Nature, vol. 437(7057), pages 426-431, September.
    • Handle: RePEc:nat:nature:v:437:y:2005:i:7057:d:10.1038_nature03952
    DOI: 10.1038/nature03952
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    Cited by:

    1. Eun-A Kwak & Christopher C. Pan & Aaron Ramonett & Sanjay Kumar & Paola Cruz-Flores & Tasmia Ahmed & Hannah R. Ortiz & Jeffrey J. Lochhead & Nathan A. Ellis & Ghassan Mouneimne & Teodora G. Georgieva , 2022. "βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Jan-Renier Moonen & James Chappell & Minyi Shi & Tsutomu Shinohara & Dan Li & Maxwell R. Mumbach & Fan Zhang & Ramesh V. Nair & Joseph Nasser & Daniel H. Mai & Shalina Taylor & Lingli Wang & Ross J. M, 2022. "KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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