TY - JOUR
T1 - Cystic fibrosis transmembrane conductance regulator is involved in polyphenol-induced swelling of the endothelial glycocalyx
AU - Peters, Wladimir
AU - Kusche-Vihrog, Kristina
AU - Oberleithner, Hans
AU - Schillers, Hermann
N1 - Funding Information:
Financial support information: This work was supported by the Deutsche Forschungsgemeinschaft (Koselleck grant OB 68/1 and KU 1496/7-1 ), the Else-Kröner-Fresenius Stiftung ( 2010_A116 ), “Innovative Medical Research” (IMF) of the University of Münster ( KU 120808 ) and by the Centre of Excellence (Cells in Motion; CIM), University of Münster. The authors would also like to thank COST Action TD1002 and COST Action BM1301 for supporting their networking activities.
Publisher Copyright:
© 2015 The Authors.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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. From the Clinical Editor: 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.
AB - 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. From the Clinical Editor: 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.
UR - http://www.scopus.com/inward/record.url?scp=84937130198&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2015.03.013
DO - 10.1016/j.nano.2015.03.013
M3 - Journal articles
C2 - 25881741
AN - SCOPUS:84937130198
SN - 1549-9634
VL - 11
SP - 1521
EP - 1530
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 6
ER -