RRC ID 27904
著者 Torisu T, Torisu K, Lee IH, Liu J, Malide D, Combs CA, Wu XS, Rovira II, Fergusson MM, Weigert R, Connelly PS, Daniels MP, Komatsu M, Cao L, Finkel T.
タイトル Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor.
ジャーナル Nat Med
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.
巻・号 19(10)
ページ 1281-7
公開日 2013-10-1
DOI 10.1038/nm.3288
PII nm.3288
PMID 24056772
PMC PMC3795899
MeSH Autophagy* Autophagy-Related Protein 5 Autophagy-Related Protein 7 Endothelial Cells / metabolism* Exocytosis Hemostasis Humans Microtubule-Associated Proteins / genetics Ubiquitin-Activating Enzymes / genetics Weibel-Palade Bodies / metabolism von Willebrand Factor / metabolism*
IF 36.13
引用数 128
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
実験動物マウス RBRC02975