TY  - JOUR
A1  - Fontijn, Ruud D.
A1  - Volger, Oscar L.
A1  - Pouw-Kraan, Tineke C. van der
A1  - Doddaballapur, Anuradha
A1  - Leyen, Thomas
A1  - Baggen, Josefien M.
A1  - Boon, Reinier
A1  - Horrevoets, Anton J. G.
T1  - Expression of nitric oxide-transporting aquaporin-1 is controlled by KLF2 and marks non-activated endothelium in vivo
T2  - PLoS One
N2  - The flow-responsive transcription factor Krüppel-like factor 2 (KLF2) maintains an anti-coagulant, anti-inflammatory endothelium with sufficient nitric oxide (NO)-bioavailability. In this study, we aimed to explore, both in vitro and in human vascular tissue, expression of the NO-transporting transmembrane pore aquaporin-1 (AQP1) and its regulation by atheroprotective KLF2 and atherogenic inflammatory stimuli. In silico analysis of gene expression profiles from studies that assessed the effects of KLF2 overexpression in vitro and atherosclerosis in vivo on endothelial cells, identifies AQP1 as KLF2 downstream gene with elevated expression in the plaque-free vessel wall. Biomechanical and pharmaceutical induction of KLF2 in vitro is accompanied by induction of AQP1. Chromosome immunoprecipitation (CHIP) confirms binding of KLF2 to the AQP1 promoter. Inflammatory stimulation of endothelial cells leads to repression of AQP1 transcription, which is restrained by KLF2 overexpression. Immunohistochemistry reveals expression of aquaporin-1 in non-activated endothelium overlying macrophage-poor intimae, irrespective whether these intimae are characterized as being plaque-free or as containing advanced plaque. We conclude that AQP1 expression is subject to KLF2-mediated positive regulation by atheroprotective shear stress and is downregulated under inflammatory conditions both in vitro and in vivo. Thus, endothelial expression of AQP1 characterizes the atheroprotected, non-inflamed vessel wall. Our data provide support for a continuous role of KLF2 in stabilizing the vessel wall via co-temporal expression of eNOS and AQP1 both preceding and during the pathogenesis of atherosclerosis.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39047
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-390470
SN  - 1932-6203
N1  - Copyright: © 2015 Fontijn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (12): e0145777
SP  - 1
EP  - 13
PB  - PLoS
CY  - Lawrence, Kan.
ER  -