title: Cystic fibrosis transmembrane conductance regulator is involved in polyphenol-induced swelling of the endothelial glycocalyx.
abstract: Previous studies show that polyphenol-rich compounds can induce a swelling of the endothelial glycocalyx (eGC). Our goal was to reveal the mechanism behind the eGC-swelling. As polyphenols are potent modulators of fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, the hypothesis was tested whether polyphenol-induced increase in CFTR activity is responsible for the eGC-swelling. The impact of the polyphenols resveratrol, (-)-epicatechin, and quercetin on nanomechanics of living endothelial GM7373 cells was monitored by AFM-nanoindentation. The tested polyphenols lead to eGC-swelling with a simultaneous decrease in cortical stiffness. EGC-swelling, but not the change in cortical stiffness, was prevented by the inhibition of CFTR. Polyphenol-induced eGC-swelling could be mimicked by cytochalasin D, an actin-depolymerizing agent. Thus, in the vascular endothelium, polyphenols induce eGC-swelling by softening cortical actin and activating CFTR. Our findings imply that CFTR plays an important role in the maintenance of vascular homeostasis and may explain the vasoprotective properties of polyphenols.
  
  
  BACKGROUND
  Many vascular problems clinically can be attributed to a dysregulation of endothelial glycocalyx (eGC). The underlying mechanism however remains unclear. In this article, the authors used nanoindentation and showed that polyphenols could swell the endothelial glycocalyx and alter its function. This investigative method can lead to further mechanistic studies of other molecular pathways.
authors.affiliation: Institute of Physiology II, University of Münster, Münster, Germany.
authors.forename: Wladimir
authors.initials: W
authors.lastname: Peters
authors.affiliation: Institute of Physiology II, University of Münster, Münster, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.affiliation: Institute of Physiology II, University of Münster, Münster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: Institute of Physiology II, University of Münster, Münster, Germany. Electronic address: Hermann.Schillers@uni-muenster.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Schillers
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D019276:Glycocalyx / Q000187:drug effects*; D018625:Microscopy, Atomic Force; D059808:Polyphenols / Q000494:pharmacology*
chemical_list: D059808:Polyphenols; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Atomic force microscopy; Cell cortex; Cortical actin; Epicatechin; Quercetin; Resveratrol