Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor

takehiro torisu, kumiko torisu, In Hye Lee, Jie Liu, Daniela Malide, Christian A. Combs, Xufeng S. Wu, Ilsa I. Rovira, Maria M. Fergusson, Roberto Weigert, Patricia S. Connelly, Mathew P. Daniels, Masaaki Komatsu, Liu Cao, Toren Finkel

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Endothelial secretion of von Willebrand factor (VWF) from intracellular organelles known as Weibel-Palade bodies (WPBs) is required for platelet adhesion to the injured vessel wall. Here we demonstrate that WPBs are often found near or within autophagosomes and that endothelial autophagosomes contain abundant VWF protein. Pharmacological inhibitors of autophagy or knockdown of the essential autophagy genes Atg5 or Atg7 inhibits the in vitro secretion of VWF. Furthermore, although mice with endothelial-specific deletion of Atg7 have normal vessel architecture and capillary density, they exhibit impaired epinephrine-stimulated VWF release, reduced levels of high-molecular weight VWF multimers and a corresponding prolongation of bleeding times. Endothelial-specific deletion of Atg5 or pharmacological inhibition of autophagic flux results in a similar in vivo alteration of hemostasis. Thus, autophagy regulates endothelial VWF secretion, and transient pharmacological inhibition of autophagic flux may be a useful strategy to prevent thrombotic events.

Original languageEnglish
Pages (from-to)1281-1287
Number of pages7
JournalNature medicine
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 1 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor'. Together they form a unique fingerprint.

  • Cite this

    torisu, T., torisu, K., Lee, I. H., Liu, J., Malide, D., Combs, C. A., Wu, X. S., Rovira, I. I., Fergusson, M. M., Weigert, R., Connelly, P. S., Daniels, M. P., Komatsu, M., Cao, L., & Finkel, T. (2013). Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor. Nature medicine, 19(10), 1281-1287. https://doi.org/10.1038/nm.3288